BioPAX pathway converted from "MyD88 dependent cascade initiated on endosome" in the Reactome database.MyD88 dependent cascade initiated on endosomeThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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>MAP kinase activationThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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.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.<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.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.<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: 10758252Converted from EntitySet in ReactomeHomologues of p-T,Y-MAPK8Reactome DB_ID: 10758230C0H5B8phospho-p-T,Y-MAPK8Reactome DB_ID: 10758224cytosolGENE ONTOLOGYGO:0005829UniProt:C0H5B8Plasmodium falciparumNCBI Taxonomy5833UniProtC0H5B8O-phospho-L-threonineMODMOD:00047O4'-phospho-L-tyrosineMODMOD:000481EQUAL427EQUALReactome Database ID Release 7510758224Database 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=10758224ReactomeR-PFA-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-PFA-194371.1Reactomehttp://www.reactome.orgQ7KQK7phospho-p-T,Y-MAPK8Reactome DB_ID: 10758228UniProt:Q7KQK7UniProtQ7KQK71EQUAL427EQUALReactome Database ID Release 7510758228Database 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=10758228ReactomeR-PFA-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-PFA-194371-2.1Reactome Database ID Release 7510758230Database 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=10758230ReactomeR-PFA-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-PFA-194371-3.1Converted from EntitySet in ReactomeHomologues of p-T183,Y185-MAPK9Reactome DB_ID: 10758240C0H5B8phospho-p-T183,Y185-MAPK9Reactome DB_ID: 10758234183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510758234Database 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=10758234ReactomeR-PFA-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-PFA-450293.1Q7KQK7phospho-p-T183,Y185-MAPK9Reactome DB_ID: 10758238183EQUAL185EQUAL1EQUAL424EQUALReactome Database ID Release 7510758238Database 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=10758238ReactomeR-PFA-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-PFA-450293-2.1Reactome Database ID Release 7510758240Database 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=10758240ReactomeR-PFA-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-PFA-450293-3.1Converted from EntitySet in ReactomeHomologues of p-T221,Y223-MAPK10Reactome DB_ID: 10758250C0H5B8phospho-p-T221,Y223-MAPK10Reactome DB_ID: 10758244221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510758244Database 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=10758244ReactomeR-PFA-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-PFA-450214.1Q7KQK7phospho-p-T221,Y223-MAPK10Reactome DB_ID: 10758248221EQUAL223EQUAL1EQUAL464EQUALReactome Database ID Release 7510758248Database 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=10758248ReactomeR-PFA-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-PFA-450214-2.1Reactome Database ID Release 7510758250Database 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=10758250ReactomeR-PFA-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-PFA-450214-3.1Reactome Database ID Release 7510758252Database 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=10758252ReactomeR-PFA-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-PFA-450226.1Converted from EntitySet in Reactomep-MAPK8,9,10Phosphorylated JNKs: MAPK8, MAPK9, MAPK10Reactome DB_ID: 10760978Converted from EntitySet in ReactomeHomologues of p-T,Y-MAPK8Reactome DB_ID: 10758915C0H5B8phospho-p-T,Y-MAPK8Reactome DB_ID: 10758911nucleoplasmGENE ONTOLOGYGO:00056541EQUAL427EQUALReactome Database ID Release 7510758911Database 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=10758911ReactomeR-PFA-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-PFA-216349.1Q7KQK7phospho-p-T,Y-MAPK8Reactome DB_ID: 107589131EQUAL427EQUALReactome Database ID Release 7510758913Database 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=10758913ReactomeR-PFA-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-PFA-216349-2.1Reactome Database ID Release 7510758915Database 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=10758915ReactomeR-PFA-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-PFA-216349-3.1Converted from EntitySet in ReactomeHomologues of p-T183,Y185-MAPK9Reactome DB_ID: 10760970C0H5B8phospho-p-T183,Y185-MAPK9Reactome DB_ID: 107609661EQUAL424EQUALReactome Database ID Release 7510760966Database 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=10760966ReactomeR-PFA-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-PFA-450319.1Q7KQK7phospho-p-T183,Y185-MAPK9Reactome DB_ID: 107609681EQUAL424EQUALReactome Database ID Release 7510760968Database 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=10760968ReactomeR-PFA-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-PFA-450319-2.1Reactome Database ID Release 7510760970Database 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=10760970ReactomeR-PFA-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-PFA-450319-3.1Converted from EntitySet in ReactomeHomologues of p-T221,Y223-MAPK10Reactome DB_ID: 10760976C0H5B8phospho-p-T221,Y223-MAPK10Reactome DB_ID: 107609721EQUAL464EQUALReactome Database ID Release 7510760972Database 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=10760972ReactomeR-PFA-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-PFA-450311.1Q7KQK7phospho-p-T221,Y223-MAPK10Reactome DB_ID: 107609741EQUAL464EQUALReactome Database ID Release 7510760974Database 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=10760974ReactomeR-PFA-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-PFA-450311-2.1Reactome Database ID Release 7510760976Database 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=10760976ReactomeR-PFA-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-PFA-450311-3.1Reactome Database ID Release 7510760978Database 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=10760978ReactomeR-PFA-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-PFA-450253.1Reactome Database ID Release 7510760980Database 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=10760980ReactomeR-PFA-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-PFA-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.12193592Pubmed2002Evidence 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 272:16657-6213130464Pubmed2003Expression 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 48:2450-60inferred from electronic annotationEVIDENCE CODEECO:0000203Reactome Database ID Release 7510773271Database 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=10773271ReactomeR-PFA-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-PFA-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. 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.Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7).16937364Pubmed2006The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs): differences revealed by gene targetingBogoyevitch, MABioessays 28:923-3426988982Pubmed2016IL-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 14:7715837794Pubmed2005Simultaneous 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 280:27728-418177321Pubmed1994The stress-activated protein kinase subfamily of c-Jun kinasesKyriakis, JMBanerjee, PNikolakaki, EDai, TRubie, EAAhmad, MFAvruch, JosephWoodgett, JRNature 369:156-6011460167Pubmed2001TAK1 is a ubiquitin-dependent kinase of MKK and IKKWang, CDeng, LHong, MAkkaraju, GRInoue, JChen, ZJNature 412:346-519851932Pubmed1998Defective T cell differentiation in the absence of Jnk1Dong, CYang, DDWysk, MWhitmarsh, AJDavis, RJFlavell, RAScience 282:2092-5activated TAK1 mediates p38 MAPK activationThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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.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.<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>ATPAdenosine 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: MAPKAPK2,3Reactome DB_ID: 10760911Converted from EntitySet in Reactomep-MAPK11/p-MAPK14p-p38 MAPK alpha/betaPhospho-MAP kinase p38 alpha/betaReactome DB_ID: 10760909Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK11Reactome DB_ID: 10760901C0H5B8phospho-p-T180,Y182-MAPK11Reactome DB_ID: 10760897180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510760897Database 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=10760897ReactomeR-PFA-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-PFA-198741.1Q7KQK7phospho-p-T180,Y182-MAPK11Reactome DB_ID: 10760899180EQUAL182EQUAL1EQUAL364EQUALReactome Database ID Release 7510760899Database 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=10760899ReactomeR-PFA-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-PFA-198741-2.1Reactome Database ID Release 7510760901Database 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=10760901ReactomeR-PFA-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-PFA-198741-3.1Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK14Reactome DB_ID: 10760907C0H5B8phospho-p-T180,Y182-MAPK14Reactome DB_ID: 107609032EQUAL360EQUALReactome Database ID Release 7510760903Database 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=10760903ReactomeR-PFA-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-PFA-446227.1Q7KQK7phospho-p-T180,Y182-MAPK14Reactome DB_ID: 107609052EQUAL360EQUALReactome Database ID Release 7510760905Database 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=10760905ReactomeR-PFA-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-PFA-446227-2.1Reactome Database ID Release 7510760907Database 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=10760907ReactomeR-PFA-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-PFA-446227-3.1Reactome Database ID Release 7510760909Database 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=10760909ReactomeR-PFA-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-PFA-198703.11Converted from EntitySet in ReactomeMAPKAP2,3MAPKAP kinaseMAPKAP2,MAPKAP3Reactome DB_ID: 10760895CPK2MAPKAPK2Q8ICR0Reactome DB_ID: 10760867UniProt:Q8ICR0CPK2UniProtQ8ICR01EQUAL400EQUALReactome Database ID Release 7510760867Database 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=10760867ReactomeR-PFA-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-PFA-450235.1Converted from EntitySet in ReactomeHomologues of MAPKAPK3Reactome DB_ID: 10760893MAPKAPK3A0A143ZWW4Reactome DB_ID: 10760869UniProt:A0A143ZWW4UniProtA0A143ZWW41EQUAL382EQUALReactome Database ID Release 7510760869Database 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=10760869ReactomeR-PFA-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-PFA-450218.1C0H5I3MAPKAPK3Reactome DB_ID: 10760871UniProt:C0H5I3UniProtC0H5I31EQUAL382EQUALReactome Database ID Release 7510760871Database 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=10760871ReactomeR-PFA-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-PFA-450218-2.1CPK1MAPKAPK3P62344Reactome DB_ID: 10760873UniProt:P62344CPK1UniProtP623441EQUAL382EQUALReactome Database ID Release 7510760873Database 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=10760873ReactomeR-PFA-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-PFA-450218-3.1Q8I2P9MAPKAPK3Reactome DB_ID: 10760875UniProt:Q8I2P9UniProtQ8I2P91EQUAL382EQUALReactome Database ID Release 7510760875Database 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=10760875ReactomeR-PFA-450218-41Reactome 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-PFA-450218-4.1Q8I534MAPKAPK3Reactome DB_ID: 10760877UniProt:Q8I534UniProtQ8I5341EQUAL382EQUALReactome Database ID Release 7510760877Database 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=10760877ReactomeR-PFA-450218-51Reactome 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-PFA-450218-5.1CPK4MAPKAPK3Q8IBS5Reactome DB_ID: 10760879UniProt:Q8IBS5CPK4UniProtQ8IBS51EQUAL382EQUALReactome Database ID Release 7510760879Database 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=10760879ReactomeR-PFA-450218-61Reactome 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-PFA-450218-6.1CPK2MAPKAPK3Q8ICR0Reactome DB_ID: 107608811EQUAL382EQUALReactome Database ID Release 7510760881Database 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=10760881ReactomeR-PFA-450218-71Reactome 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-PFA-450218-7.1Q8IDU4MAPKAPK3Reactome DB_ID: 10760883UniProt:Q8IDU4UniProtQ8IDU41EQUAL382EQUALReactome Database ID Release 7510760883Database 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=10760883ReactomeR-PFA-450218-81Reactome 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-PFA-450218-8.1Q8IDV5MAPKAPK3Reactome DB_ID: 10760885UniProt:Q8IDV5UniProtQ8IDV51EQUAL382EQUALReactome Database ID Release 7510760885Database 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=10760885ReactomeR-PFA-450218-91Reactome 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-PFA-450218-9.1Q8IID5MAPKAPK3Reactome DB_ID: 10760887UniProt:Q8IID5UniProtQ8IID51EQUAL382EQUALReactome Database ID Release 7510760887Database 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=10760887ReactomeR-PFA-450218-101Reactome 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-PFA-450218-10.1Q8IIV3MAPKAPK3Reactome DB_ID: 10760889UniProt:Q8IIV3UniProtQ8IIV31EQUAL382EQUALReactome Database ID Release 7510760889Database 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=10760889ReactomeR-PFA-450218-111Reactome 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-PFA-450218-11.1CPK3MAPKAPK3Q9NJU9Reactome DB_ID: 10760891UniProt:Q9NJU9CPK3UniProtQ9NJU91EQUAL382EQUALReactome Database ID Release 7510760891Database 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=10760891ReactomeR-PFA-450218-121Reactome 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-PFA-450218-12.1Reactome Database ID Release 7510760893Database 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=10760893ReactomeR-PFA-450218-131Reactome 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-PFA-450218-13.1Reactome Database ID Release 7510760895Database 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=10760895ReactomeR-PFA-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-PFA-450217.11Reactome Database ID Release 7510760911Database 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=10760911ReactomeR-PFA-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-PFA-450213.1p-p38 MAPK:p-MAPKAPK2/3Reactome DB_ID: 107609431Converted from EntitySet in ReactomeActive MAPKAP kinaseReactome DB_ID: 10760941Q8ICR0phospho-CPK2p-T222,S272,T334-MAPKAPK2Reactome DB_ID: 10760913222EQUAL272EQUALO-phospho-L-serineMODMOD:00046334EQUAL1EQUAL400EQUALReactome Database ID Release 7510760913Database 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=10760913ReactomeR-PFA-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-PFA-450268.1Converted from EntitySet in ReactomeHomologues of p-S,2T-MAPKAPK3Reactome DB_ID: 10760939A0A143ZWW4phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609151EQUAL382EQUALReactome Database ID Release 7510760915Database 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=10760915ReactomeR-PFA-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-PFA-450359.1C0H5I3phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609171EQUAL382EQUALReactome Database ID Release 7510760917Database 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=10760917ReactomeR-PFA-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-PFA-450359-2.1P62344phospho-CPK1p-S,2T-MAPKAPK3Reactome DB_ID: 107609191EQUAL382EQUALReactome Database ID Release 7510760919Database 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=10760919ReactomeR-PFA-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-PFA-450359-3.1Q8I2P9phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609211EQUAL382EQUALReactome Database ID Release 7510760921Database 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=10760921ReactomeR-PFA-450359-41Reactome 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-PFA-450359-4.1Q8I534phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609231EQUAL382EQUALReactome Database ID Release 7510760923Database 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=10760923ReactomeR-PFA-450359-51Reactome 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-PFA-450359-5.1Q8IBS5phospho-CPK4p-S,2T-MAPKAPK3Reactome DB_ID: 107609251EQUAL382EQUALReactome Database ID Release 7510760925Database 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=10760925ReactomeR-PFA-450359-61Reactome 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-PFA-450359-6.1Q8ICR0phospho-CPK2p-S,2T-MAPKAPK3Reactome DB_ID: 107609271EQUAL382EQUALReactome Database ID Release 7510760927Database 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=10760927ReactomeR-PFA-450359-71Reactome 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-PFA-450359-7.1Q8IDU4phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609291EQUAL382EQUALReactome Database ID Release 7510760929Database 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=10760929ReactomeR-PFA-450359-81Reactome 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-PFA-450359-8.1Q8IDV5phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609311EQUAL382EQUALReactome Database ID Release 7510760931Database 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=10760931ReactomeR-PFA-450359-91Reactome 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-PFA-450359-9.1Q8IID5phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609331EQUAL382EQUALReactome Database ID Release 7510760933Database 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=10760933ReactomeR-PFA-450359-101Reactome 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-PFA-450359-10.1Q8IIV3phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107609351EQUAL382EQUALReactome Database ID Release 7510760935Database 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=10760935ReactomeR-PFA-450359-111Reactome 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-PFA-450359-11.1Q9NJU9phospho-CPK3p-S,2T-MAPKAPK3Reactome DB_ID: 107609371EQUAL382EQUALReactome Database ID Release 7510760937Database 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=10760937ReactomeR-PFA-450359-121Reactome 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-PFA-450359-12.1Reactome Database ID Release 7510760939Database 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=10760939ReactomeR-PFA-450359-131Reactome 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-PFA-450359-13.1Reactome Database ID Release 7510760941Database 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=10760941ReactomeR-PFA-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-PFA-450261.11Reactome Database ID Release 7510760943Database 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=10760943ReactomeR-PFA-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-PFA-450254.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582ADP(3-) [ChEBI:456216]ADP(3-)ADP5'-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: #PhysicalEntity3GENE ONTOLOGYGO:0004674gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510760944Database 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=10760944Reactome Database ID Release 7510760946Database 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=10760946ReactomeR-PFA-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-PFA-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).Upon activation, p38 MAPK alpha activates MK2 by phosphorylating Thr-222, Ser-272, and Thr-334 (Ben-Levy et al. 1995). 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).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 MK2.8774846Pubmed1996A 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. 392:209-148622688Pubmed19963pK, 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. 16:868-7615287722Pubmed2004Catalysis and function of the p38 alpha.MK2a signaling complexLukas, SMKroe, RRWildeson, JPeet, GWFrego, LDavidson, WIngraham, RHPargellis, CALabadia, MEWerneburg, BGBiochemistry 43:9950-6017255097Pubmed2007Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimerTer Haar, EPrabhakar, PLiu, XLepre, CJ Biol Chem 282:9733-98626550Pubmed1996Identification 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 14:5920-3017395714Pubmed2007Molecular basis of MAPK-activated protein kinase 2:p38 assemblyWhite, APargellis, CAStudts, JMWerneburg, BGFarmer BT, 2ndProc Natl Acad Sci U S A 104:6353-812171911Pubmed2002Structure 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 277:37401-5LEFT-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.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.<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: 10760948Converted from EntitySet in ReactomeActive MAPKAP kinasep-S272,T222,T334-MAPKAPK2, p-S,2T-MAPKAPK3Reactome DB_ID: 10758663Q8ICR0phospho-CPK2p-S272,T222,T334-MAPKAPK2Reactome DB_ID: 107586111EQUAL400EQUALReactome Database ID Release 7510758611Database 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=10758611ReactomeR-PFA-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-PFA-187760.1Converted from EntitySet in ReactomeHomologues of p-S,2T-MAPKAPK3Reactome DB_ID: 10758661A0A143ZWW4phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586151EQUAL382EQUALReactome Database ID Release 7510758615Database 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=10758615ReactomeR-PFA-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-PFA-187723.1C0H5I3phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586191EQUAL382EQUALReactome Database ID Release 7510758619Database 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=10758619ReactomeR-PFA-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-PFA-187723-2.1P62344phospho-CPK1p-S,2T-MAPKAPK3Reactome DB_ID: 107586231EQUAL382EQUALReactome Database ID Release 7510758623Database 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=10758623ReactomeR-PFA-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-PFA-187723-3.1Q8I2P9phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586271EQUAL382EQUALReactome Database ID Release 7510758627Database 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=10758627ReactomeR-PFA-187723-41Reactome 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-PFA-187723-4.1Q8I534phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586311EQUAL382EQUALReactome Database ID Release 7510758631Database 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=10758631ReactomeR-PFA-187723-51Reactome 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-PFA-187723-5.1Q8IBS5phospho-CPK4p-S,2T-MAPKAPK3Reactome DB_ID: 107586351EQUAL382EQUALReactome Database ID Release 7510758635Database 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=10758635ReactomeR-PFA-187723-61Reactome 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-PFA-187723-6.1Q8ICR0phospho-CPK2p-S,2T-MAPKAPK3Reactome DB_ID: 107586391EQUAL382EQUALReactome Database ID Release 7510758639Database 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=10758639ReactomeR-PFA-187723-71Reactome 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-PFA-187723-7.1Q8IDU4phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586431EQUAL382EQUALReactome Database ID Release 7510758643Database 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=10758643ReactomeR-PFA-187723-81Reactome 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-PFA-187723-8.1Q8IDV5phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586471EQUAL382EQUALReactome Database ID Release 7510758647Database 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=10758647ReactomeR-PFA-187723-91Reactome 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-PFA-187723-9.1Q8IID5phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586511EQUAL382EQUALReactome Database ID Release 7510758651Database 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=10758651ReactomeR-PFA-187723-101Reactome 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-PFA-187723-10.1Q8IIV3phospho-p-S,2T-MAPKAPK3Reactome DB_ID: 107586551EQUAL382EQUALReactome Database ID Release 7510758655Database 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=10758655ReactomeR-PFA-187723-111Reactome 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-PFA-187723-11.1Q9NJU9phospho-CPK3p-S,2T-MAPKAPK3Reactome DB_ID: 107586591EQUAL382EQUALReactome Database ID Release 7510758659Database 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=10758659ReactomeR-PFA-187723-121Reactome 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-PFA-187723-12.1Reactome Database ID Release 7510758661Database 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=10758661ReactomeR-PFA-187723-131Reactome 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-PFA-187723-13.1Reactome Database ID Release 7510758663Database 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=10758663ReactomeR-PFA-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-PFA-187726.11Converted from EntitySet in Reactomep-p38 MAPK alpha/betaReactome DB_ID: 10758681Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK11Reactome DB_ID: 10758673C0H5B8phospho-p-T180,Y182-MAPK11Reactome DB_ID: 107586671EQUAL364EQUALReactome Database ID Release 7510758667Database 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=10758667ReactomeR-PFA-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-PFA-171009.1Q7KQK7phospho-p-T180,Y182-MAPK11Reactome DB_ID: 107586711EQUAL364EQUALReactome Database ID Release 7510758671Database 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=10758671ReactomeR-PFA-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-PFA-171009-2.1Reactome Database ID Release 7510758673Database 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=10758673ReactomeR-PFA-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-PFA-171009-3.1Converted from EntitySet in ReactomeHomologues of p-T180,Y182-MAPK14Reactome DB_ID: 10758679C0H5B8phospho-p-T180,Y182-MAPK14Reactome DB_ID: 107586752EQUAL360EQUALReactome Database ID Release 7510758675Database 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=10758675ReactomeR-PFA-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-PFA-428935.1Q7KQK7phospho-p-T180,Y182-MAPK14Reactome DB_ID: 107586772EQUAL360EQUALReactome Database ID Release 7510758677Database 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=10758677ReactomeR-PFA-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-PFA-428935-2.1Reactome Database ID Release 7510758679Database 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=10758679ReactomeR-PFA-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-PFA-428935-3.1Reactome Database ID Release 7510758681Database 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=10758681ReactomeR-PFA-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-PFA-170997.11Reactome Database ID Release 7510760948Database 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=10760948ReactomeR-PFA-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-PFA-450241.1Reactome Database ID Release 7510760950Database 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=10760950ReactomeR-PFA-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-PFA-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.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 7510773269Database 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=10773269ReactomeR-PFA-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-PFA-450302.1GENE ONTOLOGYGO:0000187p38 mitogen-activated protein kinase (MAPK) belongs to a highly conserved family of serine/threonine protein kinases. 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.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. 8622669Pubmed1996MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathwayRaingeaud, JWhitmarsh, AJBarrett, TDerijard, BDavis, RJMol Cell Biol 16:1247-558533096Pubmed1995Identification 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 270:2008-1110878576Pubmed2000p38 MAPK signalling cascades: ancient roles and new functionsMartin-Blanco, EBioessays 22:637-45MAPK targets/ Nuclear events mediated by MAP kinasesThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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.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.<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>ERKs are inactivatedThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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.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.<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 Reactomep-ERK1/2/5 dimersp-MAPK3/MAPK1/MAPK7 dimersReactome DB_ID: 10759119p-Y185,Y187 MAPK1 dimerReactome DB_ID: 10759103C0H5B8phospho-p-T185,Y187-MAPK1Reactome DB_ID: 10759101185EQUAL187EQUAL2EQUAL360EQUALReactome Database ID Release 7510759101Database 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=10759101ReactomeR-PFA-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-PFA-112354.12Reactome Database ID Release 7510759103Database 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=10759103ReactomeR-PFA-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-PFA-109856.1p-T202, Y204 MAPK3 dimerReactome DB_ID: 10759115Converted from EntitySet in ReactomeHomologues of p-T202,Y204-MAPK3Reactome DB_ID: 10759113C0H5B8phospho-p-T202,Y204-MAPK3Reactome DB_ID: 10759107202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510759107Database 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=10759107ReactomeR-PFA-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-PFA-112359.1Q7KQK7phospho-p-T202,Y204-MAPK3Reactome DB_ID: 10759111202EQUAL204EQUAL2EQUAL379EQUALReactome Database ID Release 7510759111Database 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=10759111ReactomeR-PFA-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-PFA-112359-2.1Reactome Database ID Release 7510759113Database 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=10759113ReactomeR-PFA-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-PFA-112359-3.12Reactome Database ID Release 7510759115Database 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=10759115ReactomeR-PFA-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-PFA-109845.1p-T1218, Y220 MAPK7 dimerReactome DB_ID: 10759117Converted from EntitySet in ReactomeHomologues of p-T218,Y220-MAPK7Reactome DB_ID: 10759032C0H5B8phospho-p-T218,Y220-MAPK7Reactome DB_ID: 10759028218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510759028Database 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=10759028ReactomeR-PFA-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-PFA-198738.1Q7KQK7phospho-p-T218,Y220-MAPK7Reactome DB_ID: 10759030218EQUAL220EQUAL2EQUAL816EQUALReactome Database ID Release 7510759030Database 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=10759030ReactomeR-PFA-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-PFA-198738-2.1Reactome Database ID Release 7510759032Database 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=10759032ReactomeR-PFA-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-PFA-198738-3.12Reactome Database ID Release 7510759117Database 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=10759117ReactomeR-PFA-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-PFA-9610768.1Reactome Database ID Release 7510759119Database 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=10759119ReactomeR-PFA-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-PFA-199878.1Converted from EntitySet in ReactomeERK1/2/5MAPK3/MAPK1/MAPK7 dimersReactome DB_ID: 10759141MAPK1 dimerReactome DB_ID: 10759123MAPK1C0H5B8Reactome DB_ID: 107591212EQUAL360EQUALReactome Database ID Release 7510759121Database 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=10759121ReactomeR-PFA-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-PFA-199960.12Reactome Database ID Release 7510759123Database 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=10759123ReactomeR-PFA-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-PFA-5675356.1MAPK3 dimerReactome DB_ID: 10759131Converted from EntitySet in ReactomeHomologues of MAPK3Reactome DB_ID: 10759129MAPK3C0H5B8Reactome DB_ID: 107591252EQUAL379EQUALReactome Database ID Release 7510759125Database 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=10759125ReactomeR-PFA-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-PFA-73724.1MAPK3Q7KQK7Reactome DB_ID: 107591272EQUAL379EQUALReactome Database ID Release 7510759127Database 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=10759127ReactomeR-PFA-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-PFA-73724-2.1Reactome Database ID Release 7510759129Database 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=10759129ReactomeR-PFA-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-PFA-73724-3.12Reactome Database ID Release 7510759131Database 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=10759131ReactomeR-PFA-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-PFA-5675359.1MAPK7 dimerReactome DB_ID: 10759139Converted from EntitySet in ReactomeHomologues of MAPK7Reactome DB_ID: 10759137MAPK7C0H5B8Reactome DB_ID: 107591332EQUAL816EQUALReactome Database ID Release 7510759133Database 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=10759133ReactomeR-PFA-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-PFA-199961.1MAPK7Q7KQK7Reactome DB_ID: 107591352EQUAL816EQUALReactome Database ID Release 7510759135Database 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=10759135ReactomeR-PFA-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-PFA-199961-2.1Reactome Database ID Release 7510759137Database 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=10759137ReactomeR-PFA-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-PFA-199961-3.12Reactome Database ID Release 7510759139Database 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=10759139ReactomeR-PFA-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-PFA-9610770.1Reactome Database ID Release 7510759141Database 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=10759141ReactomeR-PFA-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-PFA-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-113550.4COMPOUNDC00009ACTIVATIONConverted from EntitySet in ReactomeERK-specific DUSPReactome DB_ID: 10759442DUSP4Q8IKS8Reactome DB_ID: 10759436UniProt:Q8IKS8UniProtQ8IKS81EQUAL394EQUALReactome Database ID Release 7510759436Database 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=10759436ReactomeR-PFA-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-PFA-203794.1DUSP7Q8IKS8Reactome DB_ID: 107594381EQUAL419EQUALReactome Database ID Release 7510759438Database 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=10759438ReactomeR-PFA-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-PFA-203791.1DUSP6Q8IKS8Reactome DB_ID: 107594401EQUAL381EQUALReactome Database ID Release 7510759440Database 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=10759440ReactomeR-PFA-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-PFA-2871619.1Reactome Database ID Release 7510759442Database 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=10759442ReactomeR-PFA-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-PFA-203792.1GENE ONTOLOGYGO:0004725Reactome Database ID Release 7510759443Database 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=10759443Reactome Database ID Release 7510759445Database 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=10759445ReactomeR-PFA-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-PFA-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 7510773055Database 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=10773055ReactomeR-PFA-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-PFA-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 7510773057Database 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=10773057ReactomeR-PFA-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-PFA-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 7510773059Database 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=10773059ReactomeR-PFA-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-PFA-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. 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.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).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 16:1026-3517158707Pubmed2006Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinasesBogoyevitch, MAKobe, BMicrobiol Mol Biol Rev 70:1061-9512471242Pubmed2002Mitogen-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 85:420-4Reactome Database ID Release 7510773061Database 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=10773061ReactomeR-PFA-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-PFA-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). 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>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).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.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.The upstream signaling events in the TLR cascade that initiate and mediate the ERK signaling pathway remain unclear.11242034Pubmed2001Mammalian MAP kinase signalling cascadesChang, LKarin, MNature 410:37-4019196711Pubmed2009Selectivity of docking sites in MAPK kinasesBardwell, AJFrankson, EBardwell, LJ Biol Chem 284:13165-7311861597Pubmed2002MAP kinases in the immune responseDong, CDavis, RJFlavell, RAAnnu Rev Immunol 20:55-72Reactome Database ID Release 7510773089Database 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=10773089ReactomeR-PFA-9751381Reactome 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-PFA-975138.1TRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.22511786Pubmed2012Essential role for IKK? in production of type 1 interferons by plasmacytoid dendritic cellsPauls, EduardoShpiro, NataliaPeggie, MarkYoung, Erick RSorcek, Ronald JTan, LiChoi, Hwan GeunCohen, PJ. Biol. Chem. 287:19216-2818794297Pubmed2008The kinase activity of IL-1 receptor-associated kinase 4 is required for interleukin-1 receptor/toll-like receptor-induced TAK1-dependent NFkappaB activationFraczek, JerzyKim, Tae WhanXiao, HYao, JianhongWen, QianLi, YaliCasanova, JLPryjma, JuliuszLi, XJ. Biol. Chem. 283:31697-705Reactome Database ID Release 7510773091Database 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=10773091ReactomeR-PFA-9751551Reactome 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-PFA-975155.1Upon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I IFNs.18652679Pubmed2008Comparison of human B cell activation by TLR7 and TLR9 agonistsHanten, John AVasilakos, John PRiter, Christie LNeys, LoriLipson, Kenneth EAlkan, Sefik SBirmachu, WoubalemBMC Immunol. 9:3915276183Pubmed2004MD-2: the Toll 'gatekeeper' in endotoxin signallingGangloff, MGay, Nicholas JTrends Biochem Sci 29:294-30016497588Pubmed2006Pathogen recognition and innate immunityAkira, ShizuoUematsu, STakeuchi, OCell 124:783-80120237413Pubmed2010Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistanceCherfils-Vicini, JulienPlatonova, SophiaGillard, MélanieLaurans, LudivineValidire, PierreCaliandro, RafaeleMagdeleinat, PierreMami-Chouaib, FathiaDieu-Nosjean, Marie-CarolineFridman, Wolf-HermanDamotte, DianeSautès-Fridman, CatherineCremer, IsabelleJ. Clin. Invest. 120:1285-97