BioPAX pathway converted from "Toll Like Receptor 2 (TLR2) Cascade" in the Reactome database.Toll Like Receptor 2 (TLR2) CascadeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Toll Like Receptor TLR1:TLR2 CascadeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>MyD88:MAL(TIRAP) cascade initiated on plasma membraneThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>IRAK2 mediated activation of TAK1 complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTIRAK2 induces TRAF6 oligomerizationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TRAF6:p-IRAK2Reactome DB_ID: 10662576plasma membraneGENE ONTOLOGYGO:0005886TRAF6Q54NN4Reactome DB_ID: 10662572UniProt:Q54NN4Dictyostelium discoideumNCBI Taxonomy44689UniProtQ54NN41EQUAL522EQUALReactome Database ID Release 7510662572Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662572ReactomeR-DDI-9369551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936955.1Reactomehttp://www.reactome.org1Q54LU8phospho-p-IRAK2Reactome DB_ID: 10662574UniProt:Q54LU8UniProtQ54LU8phosphorylated residueMODMOD:006961EQUAL625EQUALReactome Database ID Release 7510662574Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662574ReactomeR-DDI-9369491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936949.11Reactome Database ID Release 7510662576Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662576ReactomeR-DDI-9369611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936961.1TRAF6Q54NN4Reactome DB_ID: 10652479cytosolGENE ONTOLOGYGO:00058291EQUAL522EQUALReactome Database ID Release 7510652479Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652479ReactomeR-DDI-1663661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-166366.12p-IRAK2:oligo-TRAF6Reactome DB_ID: 1066257821Reactome Database ID Release 7510662578Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662578ReactomeR-DDI-9369901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936990.1Reactome Database ID Release 7510662588Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662588ReactomeR-DDI-9369631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936963.1The mechanism by which IRAK-2 induces TRAF6 E3 ligase activity remains to be deciphered, but one possibility is that IRAK-2 may direct TRAF6 oligomerization.17878161Pubmed2007IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitinationKeating, SEMaloney, GMMoran, EMBowie, AGJ Biol Chem 282:33435-43inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHT6.3.2.19Auto ubiquitination of oligo-TRAF6 bound to p-IRAK2This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeUbubiquitinReactome DB_ID: 10644946Converted from EntitySet in ReactomeHomologues of RPS27A(1-76)Reactome DB_ID: 10644818ubqBRPS27A(1-76)P14794Reactome DB_ID: 10644812UniProt:P14794ubqBUniProtP147941EQUAL76EQUALReactome Database ID Release 7510644812Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644812ReactomeR-DDI-9392051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939205.1ubqCRPS27A(1-76)P14797Reactome DB_ID: 10644814UniProt:P14797ubqCUniProtP147971EQUAL76EQUALReactome Database ID Release 7510644814Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644814ReactomeR-DDI-939205-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939205-2.1ubqORPS27A(1-76)Q54CI0Reactome DB_ID: 10644816UniProt:Q54CI0ubqOUniProtQ54CI01EQUAL76EQUALReactome Database ID Release 7510644816Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644816ReactomeR-DDI-939205-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939205-3.1Reactome Database ID Release 7510644818Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644818ReactomeR-DDI-939205-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939205-4.1Converted from EntitySet in ReactomeHomologues of UBB(1-76)Reactome DB_ID: 10644832ubqDUBB(1-76)P0CG77Reactome DB_ID: 10644820UniProt:P0CG77ubqDUniProtP0CG771EQUAL76EQUALReactome Database ID Release 7510644820Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644820ReactomeR-DDI-9392141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214.1ubqFUBB(1-76)P0CG78Reactome DB_ID: 10644822UniProt:P0CG78ubqFUniProtP0CG781EQUAL76EQUALReactome Database ID Release 7510644822Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644822ReactomeR-DDI-939214-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-2.1ubqGUBB(1-76)P0CG79Reactome DB_ID: 10644824UniProt:P0CG79ubqGUniProtP0CG791EQUAL76EQUALReactome Database ID Release 7510644824Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644824ReactomeR-DDI-939214-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-3.1ubqIUBB(1-76)P0CG80Reactome DB_ID: 10644826UniProt:P0CG80ubqIUniProtP0CG801EQUAL76EQUALReactome Database ID Release 7510644826Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644826ReactomeR-DDI-939214-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-4.1ubqHUBB(1-76)P0CG81Reactome DB_ID: 10644828UniProt:P0CG81ubqHUniProtP0CG811EQUAL76EQUALReactome Database ID Release 7510644828Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644828ReactomeR-DDI-939214-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-5.1ubqJUBB(1-76)P0CG88Reactome DB_ID: 10644830UniProt:P0CG88ubqJUniProtP0CG881EQUAL76EQUALReactome Database ID Release 7510644830Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644830ReactomeR-DDI-939214-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-6.1Reactome Database ID Release 7510644832Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644832ReactomeR-DDI-939214-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939214-7.1Converted from EntitySet in ReactomeHomologues of UBB(77-152)Reactome DB_ID: 10644846ubqDUBB(77-152)P0CG77Reactome DB_ID: 1064483477EQUAL152EQUALReactome Database ID Release 7510644834Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644834ReactomeR-DDI-9392131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213.1ubqFUBB(77-152)P0CG78Reactome DB_ID: 1064483677EQUAL152EQUALReactome Database ID Release 7510644836Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644836ReactomeR-DDI-939213-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-2.1ubqGUBB(77-152)P0CG79Reactome DB_ID: 1064483877EQUAL152EQUALReactome Database ID Release 7510644838Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644838ReactomeR-DDI-939213-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-3.1ubqIUBB(77-152)P0CG80Reactome DB_ID: 1064484077EQUAL152EQUALReactome Database ID Release 7510644840Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644840ReactomeR-DDI-939213-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-4.1ubqHUBB(77-152)P0CG81Reactome DB_ID: 1064484277EQUAL152EQUALReactome Database ID Release 7510644842Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644842ReactomeR-DDI-939213-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-5.1ubqJUBB(77-152)P0CG88Reactome DB_ID: 1064484477EQUAL152EQUALReactome Database ID Release 7510644844Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644844ReactomeR-DDI-939213-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-6.1Reactome Database ID Release 7510644846Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644846ReactomeR-DDI-939213-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939213-7.1Converted from EntitySet in ReactomeHomologues of UBB(153-228)Reactome DB_ID: 10644860ubqDUBB(153-228)P0CG77Reactome DB_ID: 10644848153EQUAL228EQUALReactome Database ID Release 7510644848Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644848ReactomeR-DDI-9392301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230.1ubqFUBB(153-228)P0CG78Reactome DB_ID: 10644850153EQUAL228EQUALReactome Database ID Release 7510644850Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644850ReactomeR-DDI-939230-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-2.1ubqGUBB(153-228)P0CG79Reactome DB_ID: 10644852153EQUAL228EQUALReactome Database ID Release 7510644852Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644852ReactomeR-DDI-939230-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-3.1ubqIUBB(153-228)P0CG80Reactome DB_ID: 10644854153EQUAL228EQUALReactome Database ID Release 7510644854Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644854ReactomeR-DDI-939230-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-4.1ubqHUBB(153-228)P0CG81Reactome DB_ID: 10644856153EQUAL228EQUALReactome Database ID Release 7510644856Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644856ReactomeR-DDI-939230-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-5.1ubqJUBB(153-228)P0CG88Reactome DB_ID: 10644858153EQUAL228EQUALReactome Database ID Release 7510644858Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644858ReactomeR-DDI-939230-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-6.1Reactome Database ID Release 7510644860Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644860ReactomeR-DDI-939230-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939230-7.1Converted from EntitySet in ReactomeHomologues of UBC(229-304)Reactome DB_ID: 10644874ubqDUBC(229-304)P0CG77Reactome DB_ID: 10644862229EQUAL304EQUALReactome Database ID Release 7510644862Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644862ReactomeR-DDI-9391921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192.1ubqFUBC(229-304)P0CG78Reactome DB_ID: 10644864229EQUAL304EQUALReactome Database ID Release 7510644864Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644864ReactomeR-DDI-939192-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-2.1ubqGUBC(229-304)P0CG79Reactome DB_ID: 10644866229EQUAL304EQUALReactome Database ID Release 7510644866Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644866ReactomeR-DDI-939192-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-3.1ubqIUBC(229-304)P0CG80Reactome DB_ID: 10644868229EQUAL304EQUALReactome Database ID Release 7510644868Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644868ReactomeR-DDI-939192-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-4.1ubqHUBC(229-304)P0CG81Reactome DB_ID: 10644870229EQUAL304EQUALReactome Database ID Release 7510644870Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644870ReactomeR-DDI-939192-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-5.1ubqJUBC(229-304)P0CG88Reactome DB_ID: 10644872229EQUAL304EQUALReactome Database ID Release 7510644872Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644872ReactomeR-DDI-939192-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-6.1Reactome Database ID Release 7510644874Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644874ReactomeR-DDI-939192-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939192-7.1Converted from EntitySet in ReactomeHomologues of UBC(305-380)Reactome DB_ID: 10644888ubqDUBC(305-380)P0CG77Reactome DB_ID: 10644876305EQUAL380EQUALReactome Database ID Release 7510644876Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644876ReactomeR-DDI-9392321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232.1ubqFUBC(305-380)P0CG78Reactome DB_ID: 10644878305EQUAL380EQUALReactome Database ID Release 7510644878Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644878ReactomeR-DDI-939232-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-2.1ubqGUBC(305-380)P0CG79Reactome DB_ID: 10644880305EQUAL380EQUALReactome Database ID Release 7510644880Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644880ReactomeR-DDI-939232-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-3.1ubqIUBC(305-380)P0CG80Reactome DB_ID: 10644882305EQUAL380EQUALReactome Database ID Release 7510644882Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644882ReactomeR-DDI-939232-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-4.1ubqHUBC(305-380)P0CG81Reactome DB_ID: 10644884305EQUAL380EQUALReactome Database ID Release 7510644884Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644884ReactomeR-DDI-939232-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-5.1ubqJUBC(305-380)P0CG88Reactome DB_ID: 10644886305EQUAL380EQUALReactome Database ID Release 7510644886Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644886ReactomeR-DDI-939232-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-6.1Reactome Database ID Release 7510644888Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644888ReactomeR-DDI-939232-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939232-7.1Converted from EntitySet in ReactomeHomologues of UBC(381-456)Reactome DB_ID: 10644902ubqDUBC(381-456)P0CG77Reactome DB_ID: 10644890381EQUAL456EQUALReactome Database ID Release 7510644890Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644890ReactomeR-DDI-9391911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191.1ubqFUBC(381-456)P0CG78Reactome DB_ID: 10644892381EQUAL456EQUALReactome Database ID Release 7510644892Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644892ReactomeR-DDI-939191-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-2.1ubqGUBC(381-456)P0CG79Reactome DB_ID: 10644894381EQUAL456EQUALReactome Database ID Release 7510644894Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644894ReactomeR-DDI-939191-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-3.1ubqIUBC(381-456)P0CG80Reactome DB_ID: 10644896381EQUAL456EQUALReactome Database ID Release 7510644896Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644896ReactomeR-DDI-939191-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-4.1ubqHUBC(381-456)P0CG81Reactome DB_ID: 10644898381EQUAL456EQUALReactome Database ID Release 7510644898Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644898ReactomeR-DDI-939191-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-5.1ubqJUBC(381-456)P0CG88Reactome DB_ID: 10644900381EQUAL456EQUALReactome Database ID Release 7510644900Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644900ReactomeR-DDI-939191-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-6.1Reactome Database ID Release 7510644902Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644902ReactomeR-DDI-939191-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939191-7.1Converted from EntitySet in ReactomeHomologues of UBC(457-532)Reactome DB_ID: 10644916ubqDUBC(457-532)P0CG77Reactome DB_ID: 10644904457EQUAL532EQUALReactome Database ID Release 7510644904Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644904ReactomeR-DDI-9391841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184.1ubqFUBC(457-532)P0CG78Reactome DB_ID: 10644906457EQUAL532EQUALReactome Database ID Release 7510644906Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644906ReactomeR-DDI-939184-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-2.1ubqGUBC(457-532)P0CG79Reactome DB_ID: 10644908457EQUAL532EQUALReactome Database ID Release 7510644908Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644908ReactomeR-DDI-939184-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-3.1ubqIUBC(457-532)P0CG80Reactome DB_ID: 10644910457EQUAL532EQUALReactome Database ID Release 7510644910Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644910ReactomeR-DDI-939184-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-4.1ubqHUBC(457-532)P0CG81Reactome DB_ID: 10644912457EQUAL532EQUALReactome Database ID Release 7510644912Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644912ReactomeR-DDI-939184-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-5.1ubqJUBC(457-532)P0CG88Reactome DB_ID: 10644914457EQUAL532EQUALReactome Database ID Release 7510644914Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644914ReactomeR-DDI-939184-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-6.1Reactome Database ID Release 7510644916Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644916ReactomeR-DDI-939184-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939184-7.1Converted from EntitySet in ReactomeHomologues of UBC(533-608)Reactome DB_ID: 10644930ubqDUBC(533-608)P0CG77Reactome DB_ID: 10644918533EQUAL608EQUALReactome Database ID Release 7510644918Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644918ReactomeR-DDI-9392391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239.1ubqFUBC(533-608)P0CG78Reactome DB_ID: 10644920533EQUAL608EQUALReactome Database ID Release 7510644920Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644920ReactomeR-DDI-939239-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-2.1ubqGUBC(533-608)P0CG79Reactome DB_ID: 10644922533EQUAL608EQUALReactome Database ID Release 7510644922Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644922ReactomeR-DDI-939239-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-3.1ubqIUBC(533-608)P0CG80Reactome DB_ID: 10644924533EQUAL608EQUALReactome Database ID Release 7510644924Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644924ReactomeR-DDI-939239-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-4.1ubqHUBC(533-608)P0CG81Reactome DB_ID: 10644926533EQUAL608EQUALReactome Database ID Release 7510644926Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644926ReactomeR-DDI-939239-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-5.1ubqJUBC(533-608)P0CG88Reactome DB_ID: 10644928533EQUAL608EQUALReactome Database ID Release 7510644928Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644928ReactomeR-DDI-939239-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-6.1Reactome Database ID Release 7510644930Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644930ReactomeR-DDI-939239-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939239-7.1Converted from EntitySet in ReactomeHomologues of UBC(609-684)Reactome DB_ID: 10644944ubqDUBC(609-684)P0CG77Reactome DB_ID: 10644932609EQUAL684EQUALReactome Database ID Release 7510644932Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644932ReactomeR-DDI-9391651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165.1ubqFUBC(609-684)P0CG78Reactome DB_ID: 10644934609EQUAL684EQUALReactome Database ID Release 7510644934Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644934ReactomeR-DDI-939165-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-2.1ubqGUBC(609-684)P0CG79Reactome DB_ID: 10644936609EQUAL684EQUALReactome Database ID Release 7510644936Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644936ReactomeR-DDI-939165-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-3.1ubqIUBC(609-684)P0CG80Reactome DB_ID: 10644938609EQUAL684EQUALReactome Database ID Release 7510644938Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644938ReactomeR-DDI-939165-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-4.1ubqHUBC(609-684)P0CG81Reactome DB_ID: 10644940609EQUAL684EQUALReactome Database ID Release 7510644940Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644940ReactomeR-DDI-939165-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-5.1ubqJUBC(609-684)P0CG88Reactome DB_ID: 10644942609EQUAL684EQUALReactome Database ID Release 7510644942Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644942ReactomeR-DDI-939165-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-6.1Reactome Database ID Release 7510644944Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644944ReactomeR-DDI-939165-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-939165-7.1Reactome Database ID Release 7510644946Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10644946ReactomeR-DDI-1135951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-113595.19p-IRAK2:K63-linked pUb oligo-TRAF6Reactome DB_ID: 10662583Q54NN4K63polyUb-TRAF6Reactome DB_ID: 10662581124EQUALubiquitinylated lysineMODMOD:011481EQUAL522EQUALReactome Database ID Release 7510662581Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662581ReactomeR-DDI-9369801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936980.131Reactome Database ID Release 7510662583Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662583ReactomeR-DDI-9369881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936988.1ACTIVATIONactiveUnit: #Protein1GENE ONTOLOGYGO:0004842gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510662584Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662584Reactome Database ID Release 7510662586Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662586ReactomeR-DDI-9369421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936942.1TRAF6 possesses ubiquitin ligase activity and undergoes K-63-linked auto-ubiquitination after its oligomerization. In the first step, ubiquitin is activated by an E1 ubiquitin activating enzyme. The activated ubiquitin is transferred to a E2 conjugating enzyme (a heterodimer of proteins Ubc13 and Uev1A) forming the E2-Ub thioester. Finally, in the presence of ubiquitin-protein ligase E3 (TRAF6, a RING-domain E3), ubiquitin is attached to the target protein (TRAF6 on residue Lysine 124) through an isopeptide bond between the C-terminus of ubiquitin and the epsilon-amino group of a lysine residue in the target protein. In contrast to K-48-linked ubiquitination that leads to the proteosomal degradation of the target protein, K-63-linked polyubiquitin chains act as a scaffold to assemble protein kinase complexes and mediate their activation through proteosome-independent mechanisms. This K63 polyubiquitinated TRAF6 activates the TAK1 kinase complex.17135271Pubmed2007Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activationLamothe, BBesse, ACampos, ADWebster, WKWu, HDarnay, BGJ Biol Chem 282:4102-12LEFT-TO-RIGHT6.3.2.19Activated TRAF6 synthesizes unanchored polyubiquitin chainsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>K63polyUbReactome DB_ID: 10652776Reactome Database ID Release 7510652776Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652776ReactomeR-DDI-4501521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450152.1ACTIVATIONactiveUnit: #Protein72Reactome Database ID Release 7510662589Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662589Q54NN4K63polyUb-TRAF6Reactome DB_ID: 10660656endosome membraneGENE ONTOLOGYGO:0010008124EQUAL1EQUAL522EQUALReactome Database ID Release 7510660656Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660656ReactomeR-DDI-4502271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450227.1Reactome Database ID Release 7510662591Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10662591ReactomeR-DDI-9369861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-936986.1Polyubiquitinated TRAF6 (as E3 ubiquitin ligase) generates free K63 -linked polyubiquitin chains that non-covalently associate with ubiquitin receptors of TAB2/TAB3 regulatory proteins of the TAK1 complex, leading to the activation of the TAK1 kinase.19675569Pubmed2009Direct activation of protein kinases by unanchored polyubiquitin chainsXia, ZPSun, LChen, XPineda, GJiang, XAdhikari, AZeng, WChen, ZJNatureReactome Database ID Release 7510697851Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697851ReactomeR-DDI-9370421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-937042.1Although IRAK-1 was originally thought to be a key mediator of TRAF6 activation in the IL1R/TLR signaling (Dong W et al. 2006), recent studies showed that IRAK-2, but not IRAK-1, led to TRAF6 polyubiquitination (Keating SE et al 2007). IRAK-2 loss-of-function mutants, with mutated TRAF6-binding motifs, could no longer activate NF-kB and could no longer stimulate TRAF-6 ubiquitination (Keating SE et al 2007). Furthermore, the proxyvirus protein A52 - an inhibitor of all IL-1R/TLR pathways to NF-kB activation, was found to interact with both IRAK-2 and TRAF6, but not IRAK-1. Further work showed that A52 inhibits IRAK-2 functions, whereas association with TRAF6 results in A52-induced MAPK activation. The strong inhibition effect of A52 was also observed on the TLR3-NFkB axis and this observation led to the discovery that IRAK-2 is recruited to TLR3 to activate NF-kB (Keating SE et al 2007). Thus, A52 possibly inhibits MyD88-independent TLR3 pathways to NF-kB via targeting IRAK-2 as it does for other IL-1R/TLR pathways, although it remains unclear how IRAK-2 is involved in TLR3 signaling.<p>IRAK-2 was shown to have two TRAF6 binding motifs that are responsible for initiating TRAF6 signaling transduction (Ye H et al 2002).21606490Pubmed2011Human interleukin-1 receptor-associated kinase-2 is essential for Toll-like receptor-mediated transcriptional and post-transcriptional regulation of tumor necrosis factor alphaFlannery, Sinead MKeating, Sinead ESzymak, JoannaBowie, Andrew GJ. Biol. Chem. 286:23688-9712140561Pubmed2002Distinct molecular mechanism for initiating TRAF6 signallingYe, HArron, JRLamothe, BCirilli, MKobayashi, TShevde, NKSegal, DDzivenu, OKVologodskaia, MYim, MDu, KSingh, SPike, JWDarnay, BGChoi, YWu, HNature 418:443-716831874Pubmed2006The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4Dong, WLiu, YPeng, JChen, LZou, TXiao, HLiu, ZLi, WBu, YQi, YJ Biol Chem 281:26029-40MAP kinase activationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTActivated human JNKs migrate to nucleoplasmThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in Reactomep-MAPK8,9,10phosphorylated JNKs: MAPK8_MAPK9_MAPK10Reactome DB_ID: 10652581Converted from EntitySet in ReactomeHomologues of p-T,Y-MAPK8Reactome DB_ID: 10652543P42525phospho-erkAp-T,Y-MAPK8Reactome DB_ID: 10652529UniProt:P42525erkAUniProtP42525O-phospho-L-threonineMODMOD:00047O4'-phospho-L-tyrosineMODMOD:000481EQUAL427EQUALReactome Database ID Release 7510652529Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652529ReactomeR-DDI-1943711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-194371.1Q54US6phospho-p-T,Y-MAPK8Reactome DB_ID: 10652533UniProt:Q54US6UniProtQ54US61EQUAL427EQUALReactome Database ID Release 7510652533Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652533ReactomeR-DDI-194371-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-194371-2.1Q54V35phospho-p-T,Y-MAPK8Reactome DB_ID: 10652537UniProt:Q54V35UniProtQ54V351EQUAL427EQUALReactome Database ID Release 7510652537Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652537ReactomeR-DDI-194371-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-194371-3.1Q54V83phospho-p-T,Y-MAPK8Reactome DB_ID: 10652541UniProt:Q54V83UniProtQ54V831EQUAL427EQUALReactome Database ID Release 7510652541Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652541ReactomeR-DDI-194371-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-194371-4.1Reactome Database ID Release 7510652543Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652543ReactomeR-DDI-194371-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-194371-5.1Converted from EntitySet in ReactomeHomologues of p-T183,Y185-MAPK9Reactome DB_ID: 10652561P42525phospho-erkAp-T183,Y185-MAPK9Reactome DB_ID: 10652547183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510652547Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652547ReactomeR-DDI-4502931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450293.1Q54US6phospho-p-T183,Y185-MAPK9Reactome DB_ID: 10652551183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510652551Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652551ReactomeR-DDI-450293-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450293-2.1Q54V35phospho-p-T183,Y185-MAPK9Reactome DB_ID: 10652555183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510652555Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652555ReactomeR-DDI-450293-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450293-3.1Q54V83phospho-p-T183,Y185-MAPK9Reactome DB_ID: 10652559183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510652559Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652559ReactomeR-DDI-450293-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450293-4.1Reactome Database ID Release 7510652561Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652561ReactomeR-DDI-450293-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450293-5.1Converted from EntitySet in ReactomeHomologues of p-T221,Y223-MAPK10Reactome DB_ID: 10652579P42525phospho-erkAp-T221,Y223-MAPK10Reactome DB_ID: 10652565221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510652565Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652565ReactomeR-DDI-4502141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450214.1Q54US6phospho-p-T221,Y223-MAPK10Reactome DB_ID: 10652569221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510652569Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652569ReactomeR-DDI-450214-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450214-2.1Q54V35phospho-p-T221,Y223-MAPK10Reactome DB_ID: 10652573221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510652573Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652573ReactomeR-DDI-450214-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450214-3.1Q54V83phospho-p-T221,Y223-MAPK10Reactome DB_ID: 10652577221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510652577Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652577ReactomeR-DDI-450214-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450214-4.1Reactome Database ID Release 7510652579Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652579ReactomeR-DDI-450214-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450214-5.1Reactome Database ID Release 7510652581Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10652581ReactomeR-DDI-4502261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450226.1Converted from EntitySet in Reactomep-MAPK8,9,10Phosphorylated JNKs: MAPK8, MAPK9, MAPK10Reactome DB_ID: 10660651Converted from EntitySet in ReactomeHomologues of p-T,Y-MAPK8Reactome DB_ID: 10654127P42525phospho-erkAp-T,Y-MAPK8Reactome DB_ID: 10654119nucleoplasmGENE ONTOLOGYGO:00056541EQUAL427EQUALReactome Database ID Release 7510654119Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10654119ReactomeR-DDI-2163491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-216349.1Q54US6phospho-p-T,Y-MAPK8Reactome DB_ID: 106541211EQUAL427EQUALReactome Database ID Release 7510654121Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10654121ReactomeR-DDI-216349-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-216349-2.1Q54V35phospho-p-T,Y-MAPK8Reactome DB_ID: 106541231EQUAL427EQUALReactome Database ID Release 7510654123Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10654123ReactomeR-DDI-216349-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-216349-3.1Q54V83phospho-p-T,Y-MAPK8Reactome DB_ID: 106541251EQUAL427EQUALReactome Database ID Release 7510654125Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10654125ReactomeR-DDI-216349-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-216349-4.1Reactome Database ID Release 7510654127Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10654127ReactomeR-DDI-216349-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-216349-5.1Converted from EntitySet in ReactomeHomologues of p-T183,Y185-MAPK9Reactome DB_ID: 10660639P42525phospho-erkAp-T183,Y185-MAPK9Reactome DB_ID: 106606311EQUAL424EQUALReactome Database ID Release 7510660631Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660631ReactomeR-DDI-4503191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450319.1Q54US6phospho-p-T183,Y185-MAPK9Reactome DB_ID: 106606331EQUAL424EQUALReactome Database ID Release 7510660633Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660633ReactomeR-DDI-450319-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450319-2.1Q54V35phospho-p-T183,Y185-MAPK9Reactome DB_ID: 106606351EQUAL424EQUALReactome Database ID Release 7510660635Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660635ReactomeR-DDI-450319-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450319-3.1Q54V83phospho-p-T183,Y185-MAPK9Reactome DB_ID: 106606371EQUAL424EQUALReactome Database ID Release 7510660637Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660637ReactomeR-DDI-450319-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450319-4.1Reactome Database ID Release 7510660639Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660639ReactomeR-DDI-450319-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450319-5.1Converted from EntitySet in ReactomeHomologues of p-T221,Y223-MAPK10Reactome DB_ID: 10660649P42525phospho-erkAp-T221,Y223-MAPK10Reactome DB_ID: 106606411EQUAL464EQUALReactome Database ID Release 7510660641Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660641ReactomeR-DDI-4503111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450311.1Q54US6phospho-p-T221,Y223-MAPK10Reactome DB_ID: 106606431EQUAL464EQUALReactome Database ID Release 7510660643Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660643ReactomeR-DDI-450311-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450311-2.1Q54V35phospho-p-T221,Y223-MAPK10Reactome DB_ID: 106606451EQUAL464EQUALReactome Database ID Release 7510660645Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660645ReactomeR-DDI-450311-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450311-3.1Q54V83phospho-p-T221,Y223-MAPK10Reactome DB_ID: 106606471EQUAL464EQUALReactome Database ID Release 7510660647Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660647ReactomeR-DDI-450311-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450311-4.1Reactome Database ID Release 7510660649Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660649ReactomeR-DDI-450311-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450311-5.1Reactome Database ID Release 7510660651Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660651ReactomeR-DDI-4502531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450253.1Reactome Database ID Release 7510660653Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660653ReactomeR-DDI-4503481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450348.1c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus, where they associate and activate their target transcription factors.13130464Pubmed2003Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNKSundarrajan, MBoyle, DLChabaud-Riou, MHammaker, DFirestein, GSArthritis Rheum 48:2450-6012193592Pubmed2002Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the low density lipoprotein receptor-related protein (LRP)Lutz, CNimpf, JJenny, MBoecklinger, KEnzinger, CUtermann, GBaier-Bitterlich, GBaier, GJ Biol Chem 277:43143-519195981Pubmed1997A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.Mizukami, YYoshioka, KMorimoto, SYoshida, KJ Biol Chem 272:16657-62Reactome Database ID Release 7510697777Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697777ReactomeR-DDI-4503211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450321.1GENE ONTOLOGYGO:0007254gene ontology term for cellular processMIMI:0359C-Jun NH2 terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases, that belong to mitogen activated protein kinase family (MAPKs - also known as stress-activated protein kinases, SAPKs). The JNK pathway is activated by heat shock, or inflammatory cytokines, or UV radiation. <p>The JNKs are encoded by at least three genes: JNK1/SAPK-gamma, JNK2/SAPK-alpha and JNK3/ SAPK-beta. The first two are ubiquitously expressed, whereas the JNK3 protein is found mainly in brain and to a lesser extent in heart and testes. As a result of alternative gene splicing all cells express distinct active forms of JNK from 46 to 55 kDa in size. Sequence alignment of these different products shows homologies of >80%. In spite of this similarity, the multiple JNK isoforms differ in their ability to bind and phosphorylate different target proteins, thus leading to the distinctive cellular processes: induction of apoptosis, or enhancment of cell survival, or proliferation.<p>Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7).26988982Pubmed2016IL-17 mediates inflammatory reactions via p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cellsLi, Jing-kunNie, LinZhao, Yun-pengZhang, Yuan-qiangWang, XiaoqingWang, Shuai-shuaiLiu, YiZhao, HuaCheng, LeiJ Transl Med 14:7716937364Pubmed2006The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs): differences revealed by gene targetingBogoyevitch, MABioessays 28:923-3415837794Pubmed2005Simultaneous blockade of NFkappaB, JNK, and p38 MAPK by a kinase-inactive mutant of the protein kinase TAK1 sensitizes cells to apoptosis and affects a distinct spectrum of tumor necrosis factor [corrected] target genesThiefes, AWolter, SMushinski, JFHoffmann, EDittrich-Breiholz, OGraue, NDörrie, ASchneider, HWirth, DLuckow, BResch, KKracht, MJ Biol Chem 280:27728-419851932Pubmed1998Defective T cell differentiation in the absence of Jnk1Dong, CYang, DDWysk, MWhitmarsh, AJDavis, RJFlavell, RAScience 282:2092-511460167Pubmed2001TAK1 is a ubiquitin-dependent kinase of MKK and IKKWang, CDeng, LHong, MAkkaraju, GRInoue, JChen, ZJNature 412:346-518177321Pubmed1994The stress-activated protein kinase subfamily of c-Jun kinasesKyriakis, JMBanerjee, PNikolakaki, EDai, TRubie, EAAhmad, MFAvruch, JosephWoodgett, JRNature 369:156-60activated TAK1 mediates p38 MAPK activationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.11Active p38 MAPK phosphorylates MAPKAPK2 or 3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>p-p38 MAPK: MAPKAPK2,3Reactome DB_ID: 10660588Converted from EntitySet in ReactomeMAPKAP2,3MAPKAP kinaseMAPKAP2,MAPKAP3Reactome DB_ID: 10660586fhkAMAPKAPK2Q54BF0Reactome DB_ID: 10660578UniProt:Q54BF0fhkAUniProtQ54BF01EQUAL400EQUALReactome Database ID Release 7510660578Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660578ReactomeR-DDI-4502351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450235.1Converted from EntitySet in ReactomeHomologues of MAPKAPK3Reactome DB_ID: 10660584fhkAMAPKAPK3Q54BF0Reactome DB_ID: 106605801EQUAL382EQUALReactome Database ID Release 7510660580Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660580ReactomeR-DDI-4502181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450218.1Q54W86MAPKAPK3Reactome DB_ID: 10660582UniProt:Q54W86UniProtQ54W861EQUAL382EQUALReactome Database ID Release 7510660582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660582ReactomeR-DDI-450218-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450218-2.1Reactome Database ID Release 7510660584Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660584ReactomeR-DDI-450218-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450218-3.1Reactome Database ID Release 7510660586Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660586ReactomeR-DDI-4502171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450217.11Converted from EntitySet in Reactomep-MAPK11/p-MAPK14p-p38 MAPK alpha/betaPhospho-MAP kinase p38 alpha/betaReactome DB_ID: 10655375Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK11Reactome DB_ID: 10655363P42525phospho-erkAp-T180,Y182-MAPK11Reactome DB_ID: 10655355180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510655355Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655355ReactomeR-DDI-1987411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198741.1Q54US6phospho-p-T180,Y182-MAPK11Reactome DB_ID: 10655357180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510655357Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655357ReactomeR-DDI-198741-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198741-2.1Q54V35phospho-p-T180,Y182-MAPK11Reactome DB_ID: 10655359180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510655359Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655359ReactomeR-DDI-198741-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198741-3.1Q54V83phospho-p-T180,Y182-MAPK11Reactome DB_ID: 10655361180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510655361Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655361ReactomeR-DDI-198741-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198741-4.1Reactome Database ID Release 7510655363Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655363ReactomeR-DDI-198741-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198741-5.1Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK14Reactome DB_ID: 10655373P42525phospho-erkAp-T180,Y182-MAPK14Reactome DB_ID: 106553652EQUAL360EQUALReactome Database ID Release 7510655365Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655365ReactomeR-DDI-4462271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-446227.1Q54US6phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106553672EQUAL360EQUALReactome Database ID Release 7510655367Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655367ReactomeR-DDI-446227-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-446227-2.1Q54V35phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106553692EQUAL360EQUALReactome Database ID Release 7510655369Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655369ReactomeR-DDI-446227-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-446227-3.1Q54V83phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106553712EQUAL360EQUALReactome Database ID Release 7510655371Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655371ReactomeR-DDI-446227-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-446227-4.1Reactome Database ID Release 7510655373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655373ReactomeR-DDI-446227-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-446227-5.1Reactome Database ID Release 7510655375Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655375ReactomeR-DDI-1987031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198703.11Reactome Database ID Release 7510660588Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660588ReactomeR-DDI-4502131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450213.1ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 29358ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 7529358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29358ReactomeR-ALL-293583Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29358.3COMPOUNDC00002additional informationMIMI:03613p-p38 MAPK:p-MAPKAPK2/3Reactome DB_ID: 106606001Converted from EntitySet in ReactomeActive MAPKAP kinaseReactome DB_ID: 10660598Q54BF0phospho-fhkAp-T222,S272,T334-MAPKAPK2Reactome DB_ID: 10660590222EQUAL272EQUALO-phospho-L-serineMODMOD:00046334EQUAL1EQUAL400EQUALReactome Database ID Release 7510660590Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660590ReactomeR-DDI-4502681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450268.1Converted from EntitySet in ReactomeHomologues of p-S,2T-MAPKAPK3Reactome DB_ID: 10660596Q54BF0phospho-fhkAp-S,2T-MAPKAPK3Reactome DB_ID: 106605921EQUAL382EQUALReactome Database ID Release 7510660592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660592ReactomeR-DDI-4503591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450359.1Q54W86phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 106605941EQUAL382EQUALReactome Database ID Release 7510660594Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660594ReactomeR-DDI-450359-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450359-2.1Reactome Database ID Release 7510660596Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660596ReactomeR-DDI-450359-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450359-3.1Reactome Database ID Release 7510660598Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660598ReactomeR-DDI-4502611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450261.11Reactome Database ID Release 7510660600Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660600ReactomeR-DDI-4502541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450254.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 75113582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113582ReactomeR-ALL-1135823Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113582.3COMPOUNDC000083ACTIVATIONactiveUnit: #PhysicalEntity6GENE ONTOLOGYGO:0004674Reactome Database ID Release 7510660601Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660601Reactome Database ID Release 7510660603Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660603ReactomeR-DDI-4502221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450222.1Human p38 MAPK alpha forms a complex with MK2 even when the signaling pathway is not activated. This heterodimer is found mainly in the nucleus. The crystal structure of the unphosphorylated p38alpha-MK2 heterodimer was determined. The C-terminal regulatory domain of MK2 binds in the docking groove of p38 MAPK alpha, and the ATP-binding sites of both kinases are at the heterodimer interface (ter Haar et al. 2007).<p>Upon activation, p38 MAPK alpha activates MK2 by phosphorylating Thr-222, Ser-272, and Thr-334 (Ben-Levy et al. 1995). <p>The phosphorylation of MK2 at Thr-334 attenuates the affinity of the binary complex MK2:p38 alpha by an order of magnitude and leads to a large conformational change of an autoinhibitory domain in MK2. This conformational change unmasks not only the MK2 substrate-binding site but also the MK2 nuclear export signal (NES) thus leading to the MK2:p38 alpha translocation from the nucleus to the cytoplasm. Cytoplasmic active MK2 then phosphorylates downstream targets such as the heat-shock protein HSP27 and tristetraprolin (TTP) (Meng et al. 2002, Lukas et al. 2004, White et al. 2007).<p>MAPKAPK (MAPK-activated protein) kinase 3 (MK3, also known as 3pK) has been identified as the second p38 MAPK-activated kinase that is stimulated by different stresses (McLaughlin et al. 1996; Sithanandam et al. 1996; reviewed in Gaestel 2006). MK3 shows 75% sequence identity to MK2 and, like MK2, is activated by p38 MAPK alpha and p38 MAPK beta. MK3 phosphorylates peptide substrates with kinetic constants similar to MK2 and phosphorylates the same serine residues in HSP27 at the same relative rates as MK2 (Clifton et al. 1996) indicating an identical phosphorylation-site consensus sequence. Hence, it is assumed that its substrate spectrum is either identical to or at least overlapping with MK2.15287722Pubmed2004Catalysis and function of the p38 alpha.MK2a signaling complexLukas, SMKroe, RRWildeson, JPeet, GWFrego, LDavidson, WIngraham, RHPargellis, CALabadia, MEWerneburg, BGBiochemistry 43:9950-6012171911Pubmed2002Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear exportMeng, WSwenson, LLFitzgibbon, MJHayakawa, KTer Haar, EBehrens, AEFulghum, JRLippke, JAJ Biol Chem 277:37401-58622688Pubmed19963pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene regionSithanandam, GLatif, FDuh, F MBernal, RSmola, ULi, HKuzmin, IWixler, VGeil, LShrestha, SMol. Cell. Biol. 16:868-768774846Pubmed1996A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stressClifton, A DYoung, P RCohen, PFEBS Lett. 392:209-1417255097Pubmed2007Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimerTer Haar, EPrabhakar, PLiu, XLepre, CJ Biol Chem 282:9733-917395714Pubmed2007Molecular basis of MAPK-activated protein kinase 2:p38 assemblyWhite, APargellis, CAStudts, JMWerneburg, BGFarmer BT, 2ndProc Natl Acad Sci U S A 104:6353-88626550Pubmed1996Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinaseMcLaughlin, M MKumar, SMcDonnell, P CVan Horn, SLee, J CLivi, G PYoung, P RJ. Biol. Chem. 271:8488-928846784Pubmed1995Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2Ben-Levy, RLeighton, IADoza, YNAttwood, PMorrice, NMarshall, CJCohen, PEMBO J 14:5920-30LEFT-TO-RIGHTNuclear export of human p38 MAPK mediated by its substrate MAPKAPK2 or 3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>p-p38 MAPK: p-S272,T222,T334-MAPKAPK2, p-S,2T-MAPKAPK3Reactome DB_ID: 10660605Converted from EntitySet in Reactomep-p38 MAPK alpha/betaReactome DB_ID: 10653669Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK11Reactome DB_ID: 10653657P42525phospho-erkAp-T180,Y182-MAPK11Reactome DB_ID: 106536431EQUAL364EQUALReactome Database ID Release 7510653643Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653643ReactomeR-DDI-1710091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-171009.1Q54US6phospho-p-T180,Y182-MAPK11Reactome DB_ID: 106536471EQUAL364EQUALReactome Database ID Release 7510653647Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653647ReactomeR-DDI-171009-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-171009-2.1Q54V35phospho-p-T180,Y182-MAPK11Reactome DB_ID: 106536511EQUAL364EQUALReactome Database ID Release 7510653651Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653651ReactomeR-DDI-171009-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-171009-3.1Q54V83phospho-p-T180,Y182-MAPK11Reactome DB_ID: 106536551EQUAL364EQUALReactome Database ID Release 7510653655Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653655ReactomeR-DDI-171009-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-171009-4.1Reactome Database ID Release 7510653657Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653657ReactomeR-DDI-171009-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-171009-5.1Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK14Reactome DB_ID: 10653667P42525phospho-erkAp-T180,Y182-MAPK14Reactome DB_ID: 106536592EQUAL360EQUALReactome Database ID Release 7510653659Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653659ReactomeR-DDI-4289351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-428935.1Q54US6phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106536612EQUAL360EQUALReactome Database ID Release 7510653661Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653661ReactomeR-DDI-428935-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-428935-2.1Q54V35phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106536632EQUAL360EQUALReactome Database ID Release 7510653663Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653663ReactomeR-DDI-428935-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-428935-3.1Q54V83phospho-p-T180,Y182-MAPK14Reactome DB_ID: 106536652EQUAL360EQUALReactome Database ID Release 7510653665Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653665ReactomeR-DDI-428935-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-428935-4.1Reactome Database ID Release 7510653667Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653667ReactomeR-DDI-428935-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-428935-5.1Reactome Database ID Release 7510653669Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653669ReactomeR-DDI-1709971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-170997.11Converted from EntitySet in ReactomeActive MAPKAP kinasep-S272,T222,T334-MAPKAPK2, p-S,2T-MAPKAPK3Reactome DB_ID: 10653639Q54BF0phospho-fhkAp-S272,T222,T334-MAPKAPK2Reactome DB_ID: 106536271EQUAL400EQUALReactome Database ID Release 7510653627Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653627ReactomeR-DDI-1877601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-187760.1Converted from EntitySet in ReactomeHomologues of p-S,2T-MAPKAPK3Reactome DB_ID: 10653637Q54BF0phospho-fhkAp-S,2T-MAPKAPK3Reactome DB_ID: 106536311EQUAL382EQUALReactome Database ID Release 7510653631Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653631ReactomeR-DDI-1877231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-187723.1Q54W86phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 106536351EQUAL382EQUALReactome Database ID Release 7510653635Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653635ReactomeR-DDI-187723-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-187723-2.1Reactome Database ID Release 7510653637Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653637ReactomeR-DDI-187723-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-187723-3.1Reactome Database ID Release 7510653639Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10653639ReactomeR-DDI-1877261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-187726.11Reactome Database ID Release 7510660605Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660605ReactomeR-DDI-4502411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450241.1Reactome Database ID Release 7510660607Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660607ReactomeR-DDI-4502571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450257.1p38 MAPK alpha does not have a nuclear export signal (NES) and cannot leave the nucleus by itself, but rather needs to be associated with MAP kinase-activated protein kinase 2 (MAPKAPK2 or MK2). The NES of MAPKAPK2 facilitates the transport of both kinases from the nucleus to the cytoplasm but only after MK2 has been phosphorylated by p38alpha.<p>p38 MAPK alpha phosphorylates MK2 at Thr222, Ser272, and Thr334. The phosphorylation of Thr334 but not the kinase activity of MK2 has been demonstrated to be critical for the nuclear export of the p38 alpha - MK2 complex. Phosphorylation of Thr334 is believed to induce a conformational change in the complex exposing NES prior to interaction with the leptomycin B-sensitive nuclear export receptor.9768359Pubmed1998Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2Ben-Levy, RHooper, SWilson, RPaterson, HFMarshall, CJCurr Biol 8:1049-57Reactome Database ID Release 7510697773Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697773ReactomeR-DDI-4503021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450302.1GENE ONTOLOGYGO:0000187p38 mitogen-activated protein kinase (MAPK) belongs to a highly conserved family of serine/threonine protein kinases. <p>The p38 MAPK-dependent signaling cascade is activated by pro-inflammatory or stressful stimuli such as ultraviolet radiation, oxidative injury, heat shock, cytokines, and other pro-inflammatory stimuli. p38 MAPK exists as four isoforms (alpha, beta, gamma, and delta). Of these, p38alpha and p38beta are ubiquitously expressed while p38gamma and p38delta are differentially expressed depending on tissue type. Each isoform is activated by upstream kinases including MAP kinase kinases (MKK) 3, 4, and 6, which in turn are phosphorylated by activated TAK1 at the typical Ser-Xaa-Ala-Xaa-Thr motif in their activation loops.<p>Once p38 MAPK is phosphorylated it activates numerous downstream substrates, including MAPK-activated protein kinase-2 and 3 (MAPKAPK-2 or 3) and mitogen and stress-activated kinase-1/2 (MSK1/2). MAPKAPK-2/3 and MSK1/2 function to phosphorylate heat shock protein 27 (HSP27) and cAMP-response element binding protein transcriptional factor, respectively. Other transcription factors, including activating transcription factor 2, Elk, CHOP/GADD153, and myocyte enhancer factor 2, are known to be regulated by these kinases. 10878576Pubmed2000p38 MAPK signalling cascades: ancient roles and new functionsMartin-Blanco, EBioessays 22:637-458533096Pubmed1995Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transductionYamaguchi, KShirakabe, KShibuya, HIrie, KOishi, IUeno, NTaniguchi, TNishida, EMatsumoto, KScience 270:2008-118622669Pubmed1996MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathwayRaingeaud, JWhitmarsh, AJBarrett, TDerijard, BDavis, RJMol Cell Biol 16:1247-55MAPK targets/ Nuclear events mediated by MAP kinasesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ERK/MAPK targetsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.11ERK1/2 phosphorylates MSK1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Q8MYF1RPS6KA5Reactome DB_ID: 10655347UniProt:Q8MYF1UniProtQ8MYF11EQUAL802EQUALReactome Database ID Release 7510655347Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655347ReactomeR-DDI-1986571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198657.14Q8MYF1phospho-p-S212,S360,S376,T581-RPS6KA5Reactome DB_ID: 10655353376EQUAL581EQUAL360EQUAL212EQUAL1EQUAL802EQUALReactome Database ID Release 7510655353Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655353ReactomeR-DDI-1986831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198683.14ACTIVATIONConverted from EntitySet in Reactomep-T,Y MAPK dimersPhospho-ERK dimerReactome DB_ID: 10655474p-T202, Y204 MAPK3 dimerReactome DB_ID: 10655465Converted from EntitySet in ReactomeHomologues of p-T202,Y204-MAPK3Reactome DB_ID: 10655463P42525phospho-erkAp-T202,Y204-MAPK3Reactome DB_ID: 10655449202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510655449Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655449ReactomeR-DDI-1123591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112359.1Q54US6phospho-p-T202,Y204-MAPK3Reactome DB_ID: 10655453202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510655453Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655453ReactomeR-DDI-112359-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112359-2.1Q54V35phospho-p-T202,Y204-MAPK3Reactome DB_ID: 10655457202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510655457Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655457ReactomeR-DDI-112359-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112359-3.1Q54V83phospho-p-T202,Y204-MAPK3Reactome DB_ID: 10655461202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510655461Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655461ReactomeR-DDI-112359-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112359-4.1Reactome Database ID Release 7510655463Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655463ReactomeR-DDI-112359-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112359-5.12Reactome Database ID Release 7510655465Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655465ReactomeR-DDI-1098451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-109845.1p-Y185,Y187 MAPK1 dimerReactome DB_ID: 10655445P42525phospho-erkAp-T185,Y187-MAPK1Reactome DB_ID: 10655443185EQUAL187EQUAL2EQUAL360EQUALReactome Database ID Release 7510655443Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655443ReactomeR-DDI-1123541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-112354.12Reactome Database ID Release 7510655445Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655445ReactomeR-DDI-1098561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-109856.1Reactome Database ID Release 7510655474Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655474ReactomeR-DDI-1987011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198701.1Reactome Database ID Release 7510655475Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655475Reactome Database ID Release 7510655477Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655477ReactomeR-DDI-1987561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198756.1MSK1 (Ribosomal protein S6 kinase alpha-5) is a serine/threonine kinase that is localised in the nucleus. It contains two protein kinase domains in a single polypeptide. It can be activated 5-fold by ERK1/2 through phosphorylation at four key residues.9687510Pubmed1998Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREBDeak, MClifton, ADLucocq, LMAlessi, DREMBO J 17:4426-41LEFT-TO-RIGHT2.7.11p38MAPK phosphorylates MSK1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>44ACTIVATIONReactome Database ID Release 7510655376Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655376Reactome Database ID Release 7510655378Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655378ReactomeR-DDI-1986691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198669.1MSK1 (Ribosomal protein S6 kinase alpha-5) is a serine/threonine kinase that is localised in the nucleus. It contains two protein kinase domains in a single polypeptide. It can be activated 5-fold by p38MAPK through phosphorylation at four key residues.<br>LEFT-TO-RIGHT2.7.11ERK1/2/5 activate RSK1/2/3This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>6Converted from EntitySet in ReactomeRibosomal protein S6 kinaseReactome DB_ID: 10655416Q8MYF1RPS6KA1Reactome DB_ID: 106554101EQUAL735EQUALReactome Database ID Release 7510655410Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655410ReactomeR-DDI-1998601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199860.1Q8MYF1RPS6KA2Reactome DB_ID: 106554121EQUAL733EQUALReactome Database ID Release 7510655412Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655412ReactomeR-DDI-1998611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199861.1Q8MYF1RPS6KA3Reactome DB_ID: 106554141EQUAL740EQUALReactome Database ID Release 7510655414Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655414ReactomeR-DDI-1998691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199869.1Reactome Database ID Release 7510655416Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655416ReactomeR-DDI-1998581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199858.1Converted from EntitySet in ReactomePhospho-Ribosomal protein S6 kinaseReactome DB_ID: 10655441Q8MYF1phospho-p-4S,T359,T573-RPS6KA1Reactome DB_ID: 10655424221EQUAL363EQUAL380EQUAL732EQUAL359EQUAL573EQUAL1EQUAL735EQUALReactome Database ID Release 7510655424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655424ReactomeR-DDI-1998291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199829.1Q8MYF1phospho-p-4S,T356,T570-RPS6KA2Reactome DB_ID: 10655431218EQUAL377EQUAL730EQUAL356EQUAL570EQUAL1EQUAL733EQUALReactome Database ID Release 7510655431Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655431ReactomeR-DDI-1998711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199871.1Q8MYF1phospho-p-4S,T231,T365-RPS6KA3Reactome DB_ID: 10655439227EQUAL369EQUAL386EQUAL715EQUAL231EQUAL365EQUAL1EQUAL740EQUALReactome Database ID Release 7510655439Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655439ReactomeR-DDI-1998301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199830.1Reactome Database ID Release 7510655441Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655441ReactomeR-DDI-1998491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199849.16ACTIVATIONConverted from EntitySet in Reactomep-ERK1/2/5 dimersp-MAPK3/MAPK1/MAPK7 dimersReactome DB_ID: 10655469p-T1218, Y220 MAPK7 dimerReactome DB_ID: 10655467Converted from EntitySet in ReactomeHomologues of p-T218,Y220-MAPK7Reactome DB_ID: 10655406P42525phospho-erkAp-T218,Y220-MAPK7Reactome DB_ID: 10655398218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510655398Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655398ReactomeR-DDI-1987381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198738.1Q54US6phospho-p-T218,Y220-MAPK7Reactome DB_ID: 10655400218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510655400Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655400ReactomeR-DDI-198738-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198738-2.1Q54V35phospho-p-T218,Y220-MAPK7Reactome DB_ID: 10655402218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510655402Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655402ReactomeR-DDI-198738-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198738-3.1Q54V83phospho-p-T218,Y220-MAPK7Reactome DB_ID: 10655404218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510655404Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655404ReactomeR-DDI-198738-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198738-4.1Reactome Database ID Release 7510655406Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655406ReactomeR-DDI-198738-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198738-5.12Reactome Database ID Release 7510655467Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655467ReactomeR-DDI-96107681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-9610768.1Reactome Database ID Release 7510655469Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655469ReactomeR-DDI-1998781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199878.1Reactome Database ID Release 7510655470Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655470Reactome Database ID Release 7510655472Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655472ReactomeR-DDI-1987461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198746.1The p90 ribosomal S6 kinases (RSK1-4) comprise a family of serine/threonine kinases that lie at the terminus of the ERK pathway. RSK family members are unusual among serine/threonine kinases in that they contain two distinct kinase domains, both of which are catalytically functional . The C-terminal kinase domain is believed to be involved in autophosphorylation, a critical step in RSK activation, whereas the N-terminal kinase domain, which is homologous to members of the AGC superfamily of kinases, is responsible for the phosphorylation of all known exogenous substrates of RSK.<br>RSKs can be activated by the ERKs (ERK1, 2, 5) in the cytoplasm as well as in the nucleus, they both have cytoplasmic and nuclear substrates, and they are able to move from nucleus to cytoplasm. Efficient RSK activation by ERKs requires its interaction through a docking site located near the RSK C terminus. The mechanism of RSK activation has been studied mainly with regard to ERK1 and ERK2. RSK activation leads to the phosphorylation of four essential residues Ser239, Ser381, Ser398, and Thr590, and two additional sites, Thr377 and Ser749 (the amino acid numbering refers to RSK1). ERK is thought to play at least two roles in RSK1 activation. First, activated ERK phosphorylates RSK1 on Thr590, and possibly on Thr377 and Ser381, and second, ERK brings RSK1 into close proximity to membrane-associated kinases that may phosphorylate RSK1 on Ser381 and Ser398.<br>Moreover, RSKs and ERK1/2 form a complex that transiently dissociates upon growth factor signalling. Complex dissociation requires phosphorylation of RSK1 serine 749, a growth factor regulated phosphorylation site located near the ERK docking site. Serine 749 is phosphorylated by the N-terminal kinase domain of RSK1 itself. ERK1/2 docking to RSK2 and RSK3 is also regulated in a similar way. The length of RSK activation following growth factor stimulation depends on the duration of the RSK/ERK complex, which, in turn, differs among the different RSK isoforms. RSK1 and RSK2 readily dissociate from ERK1/2 following growth factor stimulation stimulation, but RSK3 remains associated with active ERK1/2 longer, and also remains active longer than RSK1 and RSK2. <br>12832467Pubmed2003Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activityRoux, PPRichards, SABlenis, JMol Cell Biol 23:4796-80416626623Pubmed2006The MAP kinase ERK5 binds to and phosphorylates p90 RSKRanganathan, APearson, GWChrestensen, CASturgill, TWCobb, MHArch Biochem Biophys 449:8-16LEFT-TO-RIGHTERKs are inactivated by protein phosphatase 2AThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>H2OwaterReactome DB_ID: 113518water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 75113518Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113518ReactomeR-ALL-1135183Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113518.3COMPOUNDC00001Converted from EntitySet in ReactomeERK1/2/5MAPK3/MAPK1/MAPK7 dimersReactome DB_ID: 10655658MAPK1 dimerReactome DB_ID: 10655632erkAMAPK1P42525Reactome DB_ID: 106556302EQUAL360EQUALReactome Database ID Release 7510655630Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655630ReactomeR-DDI-1999601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199960.12Reactome Database ID Release 7510655632Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655632ReactomeR-DDI-56753561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-5675356.1MAPK3 dimerReactome DB_ID: 10655644Converted from EntitySet in ReactomeHomologues of MAPK3Reactome DB_ID: 10655642erkAMAPK3P42525Reactome DB_ID: 106556342EQUAL379EQUALReactome Database ID Release 7510655634Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655634ReactomeR-DDI-737241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-73724.1MAPK3Q54US6Reactome DB_ID: 106556362EQUAL379EQUALReactome Database ID Release 7510655636Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655636ReactomeR-DDI-73724-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-73724-2.1MAPK3Q54V35Reactome DB_ID: 106556382EQUAL379EQUALReactome Database ID Release 7510655638Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655638ReactomeR-DDI-73724-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-73724-3.1MAPK3Q54V83Reactome DB_ID: 106556402EQUAL379EQUALReactome Database ID Release 7510655640Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655640ReactomeR-DDI-73724-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-73724-4.1Reactome Database ID Release 7510655642Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655642ReactomeR-DDI-73724-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-73724-5.12Reactome Database ID Release 7510655644Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655644ReactomeR-DDI-56753591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-5675359.1MAPK7 dimerReactome DB_ID: 10655656Converted from EntitySet in ReactomeHomologues of MAPK7Reactome DB_ID: 10655654erkAMAPK7P42525Reactome DB_ID: 106556462EQUAL816EQUALReactome Database ID Release 7510655646Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655646ReactomeR-DDI-1999611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199961.1MAPK7Q54US6Reactome DB_ID: 106556482EQUAL816EQUALReactome Database ID Release 7510655648Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655648ReactomeR-DDI-199961-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199961-2.1MAPK7Q54V35Reactome DB_ID: 106556502EQUAL816EQUALReactome Database ID Release 7510655650Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655650ReactomeR-DDI-199961-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199961-3.1MAPK7Q54V83Reactome DB_ID: 106556522EQUAL816EQUALReactome Database ID Release 7510655652Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655652ReactomeR-DDI-199961-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199961-4.1Reactome Database ID Release 7510655654Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655654ReactomeR-DDI-199961-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199961-5.12Reactome Database ID Release 7510655656Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655656ReactomeR-DDI-96107701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-9610770.1Reactome Database ID Release 7510655658Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655658ReactomeR-DDI-1999551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199955.1PiOrthophosphatehydrogenphosphatePhosphateInorganic PhosphateReactome DB_ID: 113550hydrogenphosphate [ChEBI:43474]hydrogenphosphatehydrogen phosphatephosphate[PO3(OH)](2-)INORGANIC PHOSPHATE GROUPHYDROGENPHOSPHATE IONHPO4(2-)[P(OH)O3](2-)ChEBICHEBI:43474Reactome Database ID Release 75113550Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113550ReactomeR-ALL-1135504Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113550.4COMPOUNDC00009ACTIVATIONPP2A-ABdeltaC complexReactome DB_ID: 10655665Converted from EntitySet in ReactomePP2A-catalytic subunit CReactome DB_ID: 10651079pho2aPPP2CAQ9XZE5Reactome DB_ID: 10651077UniProt:Q9XZE5pho2aUniProtQ9XZE51EQUAL309EQUALReactome Database ID Release 7510651077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10651077ReactomeR-DDI-1659781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-165978.1Reactome Database ID Release 7510651079Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10651079ReactomeR-DDI-1659741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-165974.11Converted from EntitySet in ReactomePP2A-subunit AReactome DB_ID: 10651088pppAPPP2R1AQ54QR9Reactome DB_ID: 10651084UniProt:Q54QR9pppAUniProtQ54QR92EQUAL589EQUALReactome Database ID Release 7510651084Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10651084ReactomeR-DDI-1659681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-165968.1Reactome Database ID Release 7510651088Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10651088ReactomeR-DDI-1659971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-165997.11psrAPPP2R5DQ54VB6Reactome DB_ID: 10655663UniProt:Q54VB6psrAUniProtQ54VB61EQUAL602EQUALReactome Database ID Release 7510655663Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655663ReactomeR-DDI-30089561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-3008956.11Reactome Database ID Release 7510655665Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655665ReactomeR-DDI-1659701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-165970.1GENE ONTOLOGYGO:0004722Reactome Database ID Release 7510655666Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655666Reactome Database ID Release 7510655668Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10655668ReactomeR-DDI-1999591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-199959.1ERKs are inactivated by the protein phosphatase 2A (PP2A). The PP2A holoenzyme is a heterotrimer that consists of a core dimer, composed of a scaffold (A) and a catalytic (C) subunit that associates with a variety of regulatory (B) subunits. The B subunits have been divided into gene families named B (or PR55), B0 (or B56 or PR61) and B00 (or PR72). Each family comprises several members. B56 family members of PP2A in particular, increase ERK dephosphorylation, without affecting its activation by MEK.<br>Induction of PP2A is involved in the extracellular signal-regulated kinase (ERK) signalling pathway, in which it provides a feedback control, as well as in a broad range of other cellular processes, including transcriptional regulation and control of the cell cycle.This diversity of functions is conferred by a diversity of regulatory subunits, the combination of which can give rise to over 50 different forms of PP2A. For example, five distinct mammalian genes encode members of the B56 family, called B56a, b, g, d and e, generating at least eight isoforms. Whether a specific holoenzyme dephosphorylates ERK and whether this activity is controlled during mitogenic stimulation is unknown.16456541Pubmed2006B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERKLetourneux, CRocher, GPorteu, FEMBO J 25:727-38ERKs are inactivatedThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT3.1.3.48ERKs are inactivated by dual-specific phosphatases (DUSPs)This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ACTIVATIONConverted from EntitySet in ReactomeERK-specific DUSPReactome DB_ID: 10656119Converted from EntitySet in ReactomeHomologues of DUSP4Reactome DB_ID: 10656089DUSP4Q54N84Reactome DB_ID: 10656062UniProt:Q54N84UniProtQ54N841EQUAL394EQUALReactome Database ID Release 7510656062Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656062ReactomeR-DDI-2037941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794.1mpl3DUSP4Q54Y32Reactome DB_ID: 10656067UniProt:Q54Y32mpl3UniProtQ54Y321EQUAL394EQUALReactome Database ID Release 7510656067Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656067ReactomeR-DDI-203794-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-2.1DUSP4Q556Y8Reactome DB_ID: 10656072UniProt:Q556Y8UniProtQ556Y81EQUAL394EQUALReactome Database ID Release 7510656072Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656072ReactomeR-DDI-203794-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-3.1mpl1DUSP4Q55CS7Reactome DB_ID: 10656077UniProt:Q55CS7mpl1UniProtQ55CS71EQUAL394EQUALReactome Database ID Release 7510656077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656077ReactomeR-DDI-203794-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-4.1mpl2DUSP4Q55CS8Reactome DB_ID: 10656082UniProt:Q55CS8mpl2UniProtQ55CS81EQUAL394EQUALReactome Database ID Release 7510656082Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656082ReactomeR-DDI-203794-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-5.1DUSP4Q8T813Reactome DB_ID: 10656087UniProt:Q8T813UniProtQ8T8131EQUAL394EQUALReactome Database ID Release 7510656087Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656087ReactomeR-DDI-203794-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-6.1Reactome Database ID Release 7510656089Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656089ReactomeR-DDI-203794-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203794-7.1Converted from EntitySet in ReactomeHomologues of DUSP7Reactome DB_ID: 10656103DUSP7Q54N84Reactome DB_ID: 106560911EQUAL419EQUALReactome Database ID Release 7510656091Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656091ReactomeR-DDI-2037911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791.1mpl3DUSP7Q54Y32Reactome DB_ID: 106560931EQUAL419EQUALReactome Database ID Release 7510656093Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656093ReactomeR-DDI-203791-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-2.1DUSP7Q556Y8Reactome DB_ID: 106560951EQUAL419EQUALReactome Database ID Release 7510656095Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656095ReactomeR-DDI-203791-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-3.1mpl1DUSP7Q55CS7Reactome DB_ID: 106560971EQUAL419EQUALReactome Database ID Release 7510656097Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656097ReactomeR-DDI-203791-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-4.1mpl2DUSP7Q55CS8Reactome DB_ID: 106560991EQUAL419EQUALReactome Database ID Release 7510656099Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656099ReactomeR-DDI-203791-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-5.1DUSP7Q8T813Reactome DB_ID: 106561011EQUAL419EQUALReactome Database ID Release 7510656101Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656101ReactomeR-DDI-203791-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-6.1Reactome Database ID Release 7510656103Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656103ReactomeR-DDI-203791-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203791-7.1Converted from EntitySet in ReactomeHomologues of DUSP6Reactome DB_ID: 10656117DUSP6Q54N84Reactome DB_ID: 106561051EQUAL381EQUALReactome Database ID Release 7510656105Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656105ReactomeR-DDI-28716191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619.1mpl3DUSP6Q54Y32Reactome DB_ID: 106561071EQUAL381EQUALReactome Database ID Release 7510656107Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656107ReactomeR-DDI-2871619-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-2.1DUSP6Q556Y8Reactome DB_ID: 106561091EQUAL381EQUALReactome Database ID Release 7510656109Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656109ReactomeR-DDI-2871619-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-3.1mpl1DUSP6Q55CS7Reactome DB_ID: 106561111EQUAL381EQUALReactome Database ID Release 7510656111Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656111ReactomeR-DDI-2871619-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-4.1mpl2DUSP6Q55CS8Reactome DB_ID: 106561131EQUAL381EQUALReactome Database ID Release 7510656113Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656113ReactomeR-DDI-2871619-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-5.1DUSP6Q8T813Reactome DB_ID: 106561151EQUAL381EQUALReactome Database ID Release 7510656115Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656115ReactomeR-DDI-2871619-61Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-6.1Reactome Database ID Release 7510656117Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656117ReactomeR-DDI-2871619-71Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-2871619-7.1Reactome Database ID Release 7510656119Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656119ReactomeR-DDI-2037921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203792.1GENE ONTOLOGYGO:0004725Reactome Database ID Release 7510656120Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656120Reactome Database ID Release 7510656122Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10656122ReactomeR-DDI-2037971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-203797.1Over 10 dual specificity phosphatases (DUSPs) active on MAP kinases are known. Among them, some possess good ERK docking sites and so are more specific for the ERKS (DUSP 3, 4, 6, 7), others are more specific for p38MAPK (DUSP1 and 10), while others do not seem to discriminate. It is noteworthy that transcription of DUSP genes is induced by growth factor signaling itself, so that these phosphatases provide feedback attenuation of signaling. Moreover, differential activation of DUSPs by different stimuli is thought to contribute to pathway specificity.17322878Pubmed2007A module of negative feedback regulators defines growth factor signalingAmit, ICitri, AShay, TLu, YKatz, MZhang, FTarcic, GSiwak, DLahad, JJacob-Hirsch, JAmariglio, NVaisman, NSegal, ERechavi, GAlon, UMills, GBDomany, EYarden, YNat Genet 39:503-12Reactome Database ID Release 7510697465Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697465ReactomeR-DDI-2026701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-202670.1MAP Kinases are inactivated by a family of protein named MAP Kinase Phosphatases (MKPs). They act through dephosphorylation of threonine and/or tyrosine residues within the signature sequence -pTXpY- located in the activation loop of MAP kinases (pT=phosphothreonine and pY=phosphotyrosine). MKPs are divided into three major categories depending on their preference for dephosphorylating; tyrosine, serine/threonine and both the tyrosine and threonine (dual specificity phoshatases or DUSPs). The tyrosine-specific MKPs include PTP-SL, STEP and HePTP, serine/threonine-specific MKPs are PP2A and PP2C, and many DUSPs acting on MAPKs are known. Activated MAP kinases trigger activation of transcription of MKP genes. Therefore, MKPs provide a negative feedback regulatory mechanism on MAPK signaling, by inactivating MAPKs via dephosphorylation, in the cytoplasm and the nucleus. Some MKPs are more specific for ERKs, others for JNK or p38MAPK.15115656Pubmed2004Structure and regulation of MAPK phosphatasesFarooq, AZhou, MMCell Signal 16:769-79Reactome Database ID Release 7510697393Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697393ReactomeR-DDI-1987531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-198753.1ERK/MAPK kinases have a number of targets within the nucleus, usually transcription factors or other kinases. The best known targets, ELK1, ETS1, ATF2, MITF, MAPKAPK2, MSK1, RSK1/2/3 and MEF2 are annotated here.Reactome Database ID Release 7510697395Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697395ReactomeR-DDI-4502821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450282.1MAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or negatively regulate substrate, and thus entire signaling cascade activity. <p>The major cytosolic target of activated ERKs are RSKs (90 kDa Ribosomal protein S6 Kinase). Active RSKs translocates to the nucleus and phosphorylates such factors as c-Fos(on Ser362), SRF (Serum Response Factor) at Ser103, and CREB (Cyclic AMP Response Element-Binding protein) at Ser133. In the nucleus activated ERKs phosphorylate many other targets such as MSKs (Mitogen- and Stress-activated protein kinases), MNK (MAP interacting kinase) and Elk1 (on Serine383 and Serine389). ERK can directly phosphorylate CREB and also AP-1 components c-Jun and c-Fos. Another important target of ERK is NF-KappaB. Recent studies reveals that nuclear pore proteins are direct substrates for ERK (Kosako H et al, 2009). Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors.</p><p>Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1).</p><p>JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Other adaptor and scaffold proteins have also been characterized as nonnuclear substrates of JNK. 19767751Pubmed2009Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transportKosako, HYamaguchi, NAranami, CUshiyama, MKose, SImamoto, NTaniguchi, HNishida, EHattori, SNat Struct Mol Biol 16:1026-3512471242Pubmed2002Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinasesJohnson, GLLapadat, RScience 298:1911-216393692Pubmed2006The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functionsYoon, SSeger, RGrowth Factors 24:21-4417637696Pubmed2007Coordinating TLR-activated signaling pathways in cells of the immune systemBanerjee, AGerondakis, SImmunol Cell Biol 85:420-417158707Pubmed2006Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinasesBogoyevitch, MAKobe, BMicrobiol Mol Biol Rev 70:1061-95Reactome Database ID Release 7510697397Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697397ReactomeR-DDI-4502941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-450294.1GENE ONTOLOGYGO:0051403The mitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascade transduces signals from the cell membrane to the nucleus in response to a wide range of stimuli (Chang and Karin, 2001; Johnson et al, 2002). <p>There are three major groups of MAP kinases<ul><li>the extracellular signal-regulated protein kinases ERK1/2, <li>the p38 MAP kinase<li> and the c-Jun NH-terminal kinases JNK.</ul><p>ERK1 and ERK2 are activated in response to growth stimuli. Both JNKs and p38-MAPK are activated in response to a variety of cellular and environmental stresses. The MAP kinases are activated by dual phosphorylation of Thr and Tyr within the tripeptide motif Thr-Xaa-Tyr. The sequence of this tripeptide motif is different in each group of MAP kinases: ERK (Thr-Glu-Tyr); p38 (Thr-Gly-Tyr); and JNK (Thr-Pro-Tyr).<p>MAPK activation is mediated by signal transduction in the conserved three-tiered kinase cascade: MAPKKKK (MAP4K or MKKKK or MAPKKK Kinase) activates the MAPKKK. The MAPKKKs then phosphorylates a dual-specificity protein kinase MAPKK, which in turn phosphorylates the MAPK.<p>The dual specificity MAP kinase kinases (MAPKK or MKK) differ for each group of MAPK. The ERK MAP kinases are activated by the MKK1 and MKK2; the p38 MAP kinases are activated by MKK3, MKK4, and MKK6; and the JNK pathway is activated by MKK4 and MKK7. The ability of MAP kinase kinases (MKKs, or MEKs) to recognize their cognate MAPKs is facilitated by a short docking motif (the D-site) in the MKK N-terminus, which binds to a complementary region on the MAPK. MAPKs then recognize many of their targets using the same strategy, because many MAPK substrates also contain D-sites.<p>The upstream signaling events in the TLR cascade that initiate and mediate the ERK signaling pathway remain unclear.11861597Pubmed2002MAP kinases in the immune responseDong, CDavis, RJFlavell, RAAnnu Rev Immunol 20:55-7211242034Pubmed2001Mammalian MAP kinase signalling cascadesChang, LKarin, MNature 410:37-4019196711Pubmed2009Selectivity of docking sites in MAPK kinasesBardwell, AJFrankson, EBardwell, LJ Biol Chem 284:13165-73Reactome Database ID Release 7510697425Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697425ReactomeR-DDI-1660581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-166058.1GENE ONTOLOGYGO:0002755The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects.15276183Pubmed2004MD-2: the Toll 'gatekeeper' in endotoxin signallingGangloff, MGay, Nicholas JTrends Biochem Sci 29:294-300Reactome Database ID Release 7510697431Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697431ReactomeR-DDI-1681791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-168179.1GENE ONTOLOGYGO:0038123TLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial triacylated lipoproteins and peptides, amongst others, triggering up-regulation of nuclear factor-kappaB production and apoptotic cascades. Such cooperation between TLR1 and TLR2 on the cell surface of normal human peripheral blood mononuclear cells, for instance, leads to the activation of pro-inflammatory cytokine secretion (Sandor et al. 2003).12975352Pubmed2003Importance of extra- and intracellular domains of TLR1 and TLR2 in NFkappa B signalingSandor, FLatz, ERe, FMandell, LRepik, GGolenbock, DTEspevik, TKurt-Jones, EAFinberg, RWJ Cell Biol 162:1099-110Toll Like Receptor TLR6:TLR2 CascadeThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome Database ID Release 7510697427Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697427ReactomeR-DDI-1681881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-168188.1GENE ONTOLOGYGO:0038124TLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recognizing peptidoglycan wall products from Gram-positive bacteria, as well as Mycobacterial diacylated lipopeptides. In particular, TLR6 appears to participate in discriminating the subtle differences between dipalmitoyl and tripalmitoyl cysteinyl residues (Okusawa et al. 2004).14977973Pubmed2004Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6Okusawa, TFujita, MNakamura, JInto, TYasuda, MYoshimura, AHara, YHasebe, AGolenbock, DTMorita, MKuroki, YOgawa, TShibata, KInfect Immun 72:1657-65Reactome Database ID Release 7510697429Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10697429ReactomeR-DDI-1814381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DDI-181438.1GENE ONTOLOGYGO:0034134TLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at least some other TLR2 ligands may be assisted by additional accessory proteins, particularly in association with TLR1 or TLR6. TLR2 is expressed constitutively on macrophages, dendritic cells, and B cells, and can be induced in some other cell types, including epithelial cells. TLR1 and TLR6, on the other hand, are expressed almost ubiquitously (Muzio et al. 2000). TLR2 may be a sensor and inductor of specific defense processes, including oxidative stress and cellular necrosis initially spurred by microbial compounds.10820283Pubmed2000Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cellsMuzio, MBosisio, DPolentarutti, ND'amico, GStoppacciaro, AMancinelli, Rvan't Veer, CPenton-Rol, GRuco, LPAllavena, PMantovani, AJ Immunol 164:5998-6004