BioPAX pathway converted from "Oxidative Stress Induced Senescence" in the Reactome database. Oxidative Stress Induced Senescence 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> LEFT-TO-RIGHT 2.7.11.1 MAP3K5 phosphorylates MKK3 and MKK6 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> Converted from EntitySet in Reactome MKK3, MKK6 MAP2K3,MAP2K6 Reactome DB_ID: 10723950 Converted from EntitySet in Reactome Homologues of MAP2K3 Reactome DB_ID: 10723946 strd-1 MAP2K3 G5ECN5 Reactome DB_ID: 10723932 cytosol GENE ONTOLOGY GO:0005829 UniProt:G5ECN5 strd-1 Caenorhabditis elegans NCBI Taxonomy 6239 UniProt G5ECN5 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723932 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723932 Reactome R-CEL-168051 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051.1 Reactome http://www.reactome.org sek-1 MAP2K3 G5EDF7 Reactome DB_ID: 10723934 UniProt:G5EDF7 sek-1 UniProt G5EDF7 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723934 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723934 Reactome R-CEL-168051-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-2.1 jkk-1 MAP2K3 G5EDT6 Reactome DB_ID: 10723936 UniProt:G5EDT6 jkk-1 UniProt G5EDT6 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723936 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723936 Reactome R-CEL-168051-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-3.1 mek-1 MAP2K3 Q21307 Reactome DB_ID: 10723938 UniProt:Q21307 mek-1 UniProt Q21307 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723938 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723938 Reactome R-CEL-168051-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-4.1 sek-5 MAP2K3 Q58AU7 Reactome DB_ID: 10723940 UniProt:Q58AU7 sek-5 UniProt Q58AU7 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723940 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723940 Reactome R-CEL-168051-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-5.1 sek-4 MAP2K3 Q58AU8 Reactome DB_ID: 10723942 UniProt:Q58AU8 sek-4 UniProt Q58AU8 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723942 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723942 Reactome R-CEL-168051-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-6.1 sek-3 MAP2K3 Q8MPS3 Reactome DB_ID: 10723944 UniProt:Q8MPS3 sek-3 UniProt Q8MPS3 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723944 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723944 Reactome R-CEL-168051-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-7.1 Reactome Database ID Release 81 10723946 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723946 Reactome R-CEL-168051-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168051-8.1 mek-1 MAP2K6 Q21307 Reactome DB_ID: 10723948 1 EQUAL 334 EQUAL Reactome Database ID Release 81 10723948 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723948 Reactome R-CEL-167998 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167998.1 Reactome Database ID Release 81 10723950 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723950 Reactome R-CEL-167916 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167916.1 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 81 113592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this 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-113592.5 COMPOUND C00002 additional information MI MI:0361 2 Converted from EntitySet in Reactome p-MKK3,p-MKK6 p-S189,T193-MAP2K3, p-S207,T211-MAP2K6 Reactome DB_ID: 10723889 Converted from EntitySet in Reactome Homologues of p-S189,T193-MAP2K3 Reactome DB_ID: 10723883 G5ECN5 phospho-strd-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723839 189 EQUAL O-phospho-L-serine MOD MOD:00046 193 EQUAL O-phospho-L-threonine MOD MOD:00047 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723839 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723839 Reactome R-CEL-167955 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955.1 G5EDF7 phospho-sek-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723846 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723846 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723846 Reactome R-CEL-167955-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-2.1 G5EDT6 phospho-jkk-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723853 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723853 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723853 Reactome R-CEL-167955-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-3.1 Q21307 phospho-mek-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723860 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723860 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723860 Reactome R-CEL-167955-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-4.1 Q58AU7 phospho-sek-5 p-S189,T193-MAP2K3 Reactome DB_ID: 10723867 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723867 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723867 Reactome R-CEL-167955-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-5.1 Q58AU8 phospho-sek-4 p-S189,T193-MAP2K3 Reactome DB_ID: 10723874 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723874 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723874 Reactome R-CEL-167955-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-6.1 Q8MPS3 phospho-sek-3 p-S189,T193-MAP2K3 Reactome DB_ID: 10723881 189 EQUAL 193 EQUAL 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723881 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723881 Reactome R-CEL-167955-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-7.1 Reactome Database ID Release 81 10723883 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723883 Reactome R-CEL-167955-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167955-8.1 Q21307 phospho-mek-1 p-S207,T211-MAP2K6 Reactome DB_ID: 10723887 207 EQUAL 211 EQUAL 1 EQUAL 334 EQUAL Reactome Database ID Release 81 10723887 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723887 Reactome R-CEL-206255 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-206255.1 Reactome Database ID Release 81 10723889 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723889 Reactome R-CEL-167984 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167984.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 81 29370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370 Reactome R-ALL-29370 5 Reactome stable identifier. Use this 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-29370.5 COMPOUND C00008 2 ACTIVATION nsy-1 MAP3K5 Q21029 Reactome DB_ID: 10741633 UniProt:Q21029 nsy-1 UniProt Q21029 1 EQUAL 1374 EQUAL Reactome Database ID Release 81 10741633 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10741633 Reactome R-CEL-167709 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-167709.1 GENE ONTOLOGY GO:0004674 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 81 10741634 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10741634 Reactome Database ID Release 81 10741636 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10741636 Reactome R-CEL-3228469 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-3228469.1 MAP3K5 (ASK1) phosphorylates and activates MAP2K3 (MKK3) and MAP2K6 (MKK6) (Ichijo et al. 1997). A conserved docking site, DVD, at the C-terminus of MAP2K3 and MAP2K6 is needed for the interaction with MAP3K5 and MAP3K5-mediated activation (Takekawa et al. 2005). 8974401 Pubmed 1997 Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways Ichijo, H Nishida, E Irie, K ten Dijke, P Saitoh, M Moriguchi, T Takagi, M Matsumoto, K Miyazono, K Gotoh, Y Science 275:90-4 15866172 Pubmed 2005 Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases Takekawa, Mutsuhiro Tatebayashi, Kazuo Saito, Haruo Mol. Cell 18:295-306 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT Phosphorylated MKK3/MKK6 migrates to nucleus 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> Converted from EntitySet in Reactome p-MKK3,p-MKK6 p-S189,T193-MAP2K3, p-S207,T211-MAP2K6 Reactome DB_ID: 10723909 Converted from EntitySet in Reactome Homologues of p-S189,T193-MAP2K3 Reactome DB_ID: 10723905 G5ECN5 phospho-strd-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723891 nucleoplasm GENE ONTOLOGY GO:0005654 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723891 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723891 Reactome R-CEL-450229 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229.1 G5EDF7 phospho-sek-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723893 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723893 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723893 Reactome R-CEL-450229-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-2.1 G5EDT6 phospho-jkk-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723895 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723895 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723895 Reactome R-CEL-450229-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-3.1 Q21307 phospho-mek-1 p-S189,T193-MAP2K3 Reactome DB_ID: 10723897 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723897 Reactome R-CEL-450229-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-4.1 Q58AU7 phospho-sek-5 p-S189,T193-MAP2K3 Reactome DB_ID: 10723899 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723899 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723899 Reactome R-CEL-450229-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-5.1 Q58AU8 phospho-sek-4 p-S189,T193-MAP2K3 Reactome DB_ID: 10723901 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723901 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723901 Reactome R-CEL-450229-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-6.1 Q8MPS3 phospho-sek-3 p-S189,T193-MAP2K3 Reactome DB_ID: 10723903 1 EQUAL 347 EQUAL Reactome Database ID Release 81 10723903 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723903 Reactome R-CEL-450229-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-7.1 Reactome Database ID Release 81 10723905 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723905 Reactome R-CEL-450229-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450229-8.1 Q21307 phospho-mek-1 p-S207,T211-MAP2K6 Reactome DB_ID: 10723907 1 EQUAL 334 EQUAL Reactome Database ID Release 81 10723907 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723907 Reactome R-CEL-450258 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450258.1 Reactome Database ID Release 81 10723909 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723909 Reactome R-CEL-450343 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450343.1 Reactome Database ID Release 81 10723911 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723911 Reactome R-CEL-450296 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450296.1 The p38 activators MKK3 (MAP2K3) and MKK6 (MAP2K6) were present in both the nucleus and the cytoplasm, consistent with a role in activating p38 in the nucleus. 7535770 Pubmed 1995 Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine Raingeaud, J Gupta, S Rogers, JS Dickens, M Han, J Ulevitch, RJ Davis, RJ J Biol Chem 270:7420-6 9768359 Pubmed 1998 Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 Ben-Levy, R Hooper, S Wilson, R Paterson, HF Marshall, CJ Curr Biol 8:1049-57 LEFT-TO-RIGHT 2.7.12.2 Activated human MKK3/MKK6 phosphorylates p38 MAPK complexed with MAPKAPK2 or MAPKAPK3 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> ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 29358 Reactome Database ID Release 81 29358 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29358 Reactome R-ALL-29358 3 Reactome stable identifier. Use this 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-29358.3 COMPOUND C00002 2 p38 MAPK:MAPKAPK2,3 Reactome DB_ID: 10723925 Converted from EntitySet in Reactome MAPKAP2,3 MAPKAP kinase MAPKAP2,MAPKAP3 Reactome DB_ID: 10723811 Converted from EntitySet in Reactome Homologues of MAPKAPK2 Reactome DB_ID: 10723807 mak-1 MAPKAPK2 Q21360 Reactome DB_ID: 10723803 UniProt:Q21360 mak-1 UniProt Q21360 1 EQUAL 400 EQUAL Reactome Database ID Release 81 10723803 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723803 Reactome R-CEL-450235 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450235.1 mak-2 MAPKAPK2 Q965G5 Reactome DB_ID: 10723805 UniProt:Q965G5 mak-2 UniProt Q965G5 1 EQUAL 400 EQUAL Reactome Database ID Release 81 10723805 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723805 Reactome R-CEL-450235-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450235-2.1 Reactome Database ID Release 81 10723807 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723807 Reactome R-CEL-450235-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450235-3.1 mak-2 MAPKAPK3 Q965G5 Reactome DB_ID: 10723809 1 EQUAL 382 EQUAL Reactome Database ID Release 81 10723809 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723809 Reactome R-CEL-450218 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450218.1 Reactome Database ID Release 81 10723811 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723811 Reactome R-CEL-450217 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450217.1 1 Converted from EntitySet in Reactome MAPK14,MAPK11 MAP kinase p38 alpha/beta Reactome DB_ID: 10723923 Converted from EntitySet in Reactome Homologues of MAPK11 Reactome DB_ID: 10723919 pmk-3 MAPK11 O44514 Reactome DB_ID: 10723913 UniProt:O44514 pmk-3 UniProt O44514 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10723913 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723913 Reactome R-CEL-203790 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-203790.1 pmk-1 MAPK11 Q17446 Reactome DB_ID: 10723915 UniProt:Q17446 pmk-1 UniProt Q17446 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10723915 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723915 Reactome R-CEL-203790-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-203790-2.1 pmk-2 MAPK11 Q8MXI4 Reactome DB_ID: 10723917 UniProt:Q8MXI4 pmk-2 UniProt Q8MXI4 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10723917 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723917 Reactome R-CEL-203790-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-203790-3.1 Reactome Database ID Release 81 10723919 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723919 Reactome R-CEL-203790-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-203790-4.1 pmk-1 MAPK14 Q17446 Reactome DB_ID: 10723921 2 EQUAL 360 EQUAL Reactome Database ID Release 81 10723921 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723921 Reactome R-CEL-446223 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-446223.1 Reactome Database ID Release 81 10723923 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723923 Reactome R-CEL-203795 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-203795.1 1 Reactome Database ID Release 81 10723925 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723925 Reactome R-CEL-450269 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450269.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 113582 Reactome Database ID Release 81 113582 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113582 Reactome R-ALL-113582 3 Reactome stable identifier. Use this 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-113582.3 COMPOUND C00008 2 p-p38 MAPK: MAPKAPK2,3 Reactome DB_ID: 10723813 Converted from EntitySet in Reactome p-MAPK11/p-MAPK14 p-p38 MAPK alpha/beta Phospho-MAP kinase p38 alpha/beta Reactome DB_ID: 10707523 Converted from EntitySet in Reactome Homologues of p-T180,Y182-MAPK11 Reactome DB_ID: 10707519 O44514 phospho-pmk-3 p-T180,Y182-MAPK11 Reactome DB_ID: 10707503 180 EQUAL 182 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10707503 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707503 Reactome R-CEL-198741 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-198741.1 Q17446 phospho-pmk-1 p-T180,Y182-MAPK11 Reactome DB_ID: 10707510 180 EQUAL 182 EQUAL 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10707510 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707510 Reactome R-CEL-198741-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-198741-2.1 Q8MXI4 phospho-pmk-2 p-T180,Y182-MAPK11 Reactome DB_ID: 10707517 180 EQUAL 182 EQUAL 1 EQUAL 364 EQUAL Reactome Database ID Release 81 10707517 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707517 Reactome R-CEL-198741-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-198741-3.1 Reactome Database ID Release 81 10707519 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707519 Reactome R-CEL-198741-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-198741-4.1 Q17446 phospho-pmk-1 p-T180,Y182-MAPK14 Reactome DB_ID: 10707521 2 EQUAL 360 EQUAL Reactome Database ID Release 81 10707521 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707521 Reactome R-CEL-446227 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-446227.1 Reactome Database ID Release 81 10707523 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707523 Reactome R-CEL-198703 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-198703.1 1 1 Reactome Database ID Release 81 10723813 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723813 Reactome R-CEL-450213 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450213.1 ACTIVATION GENE ONTOLOGY GO:0004708 Reactome Database ID Release 81 10723926 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723926 Reactome Database ID Release 81 10723928 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723928 Reactome R-CEL-450333 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450333.1 The MAPK level components of this cascade are p38MAPK-alpha, -beta, -gamma and -sigma. All of those isoforms are activated by phosphorylation of the Thr and Tyr in the Thr-Gly-Tyr motif in their activation loops. 8622669 Pubmed 1996 MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway Raingeaud, J Whitmarsh, AJ Barrett, T Derijard, B Davis, RJ Mol Cell Biol 16:1247-55 LEFT-TO-RIGHT 2.7.11.1 Active p38 MAPK phosphorylates MAPKAPK2 or 3 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> 3 3 p-p38 MAPK:p-MAPKAPK2/3 Reactome DB_ID: 10723825 1 Converted from EntitySet in Reactome Active MAPKAP kinase Reactome DB_ID: 10723823 Converted from EntitySet in Reactome Homologues of p-T222,S272,T334-MAPKAPK2 Reactome DB_ID: 10723819 Q21360 phospho-mak-1 p-T222,S272,T334-MAPKAPK2 Reactome DB_ID: 10723815 222 EQUAL 272 EQUAL 334 EQUAL 1 EQUAL 400 EQUAL Reactome Database ID Release 81 10723815 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723815 Reactome R-CEL-450268 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450268.1 Q965G5 phospho-mak-2 p-T222,S272,T334-MAPKAPK2 Reactome DB_ID: 10723817 222 EQUAL 272 EQUAL 334 EQUAL 1 EQUAL 400 EQUAL Reactome Database ID Release 81 10723817 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723817 Reactome R-CEL-450268-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450268-2.1 Reactome Database ID Release 81 10723819 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723819 Reactome R-CEL-450268-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450268-3.1 Q965G5 phospho-mak-2 p-S,2T-MAPKAPK3 Reactome DB_ID: 10723821 1 EQUAL 382 EQUAL Reactome Database ID Release 81 10723821 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723821 Reactome R-CEL-450359 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450359.1 Reactome Database ID Release 81 10723823 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723823 Reactome R-CEL-450261 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450261.1 1 Reactome Database ID Release 81 10723825 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723825 Reactome R-CEL-450254 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450254.1 ACTIVATION activeUnit: #PhysicalEntity6 Reactome Database ID Release 81 10723826 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723826 Reactome Database ID Release 81 10723828 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723828 Reactome R-CEL-450222 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450222.1 Human 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. 17395714 Pubmed 2007 Molecular basis of MAPK-activated protein kinase 2:p38 assembly White, A Pargellis, CA Studts, JM Werneburg, BG Farmer BT, 2nd Proc Natl Acad Sci U S A 104:6353-8 8774846 Pubmed 1996 A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress Clifton, A D Young, P R Cohen, P FEBS Lett. 392:209-14 12171911 Pubmed 2002 Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export Meng, W Swenson, LL Fitzgibbon, MJ Hayakawa, K Ter Haar, E Behrens, AE Fulghum, JR Lippke, JA J Biol Chem 277:37401-5 8626550 Pubmed 1996 Identification of mitogen-activated protein (MAP) kinase-activated protein kinase-3, a novel substrate of CSBP p38 MAP kinase McLaughlin, M M Kumar, S McDonnell, P C Van Horn, S Lee, J C Livi, G P Young, P R J. Biol. Chem. 271:8488-92 8846784 Pubmed 1995 Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2 Ben-Levy, R Leighton, IA Doza, YN Attwood, P Morrice, N Marshall, CJ Cohen, P EMBO J 14:5920-30 15287722 Pubmed 2004 Catalysis and function of the p38 alpha.MK2a signaling complex Lukas, SM Kroe, RR Wildeson, J Peet, GW Frego, L Davidson, W Ingraham, RH Pargellis, CA Labadia, ME Werneburg, BG Biochemistry 43:9950-60 17255097 Pubmed 2007 Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer Ter Haar, E Prabhakar, P Liu, X Lepre, C J Biol Chem 282:9733-9 8622688 Pubmed 1996 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region Sithanandam, G Latif, F Duh, F M Bernal, R Smola, U Li, H Kuzmin, I Wixler, V Geil, L Shrestha, S Mol. Cell. Biol. 16:868-76 LEFT-TO-RIGHT 2.7.11 Phosphorylation of human JNKs by activated MKK4/MKK7 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> Converted from EntitySet in Reactome MAPK8,9,10 JNKs: MAPK8_MAPK9_MAPK10 Reactome DB_ID: 10707605 jnk-1 MAPK8 Q8WQG9 Reactome DB_ID: 10707587 UniProt:Q8WQG9 jnk-1 UniProt Q8WQG9 1 EQUAL 427 EQUAL Reactome Database ID Release 81 10707587 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707587 Reactome R-CEL-168141 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168141.1 Converted from EntitySet in Reactome Homologues of MAPK9 Reactome DB_ID: 10707595 kgb-2 MAPK9 H2KZI0 Reactome DB_ID: 10707589 UniProt:H2KZI0 kgb-2 UniProt H2KZI0 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707589 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707589 Reactome R-CEL-450355 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450355.1 kgb-1 MAPK9 O44408 Reactome DB_ID: 10707591 UniProt:O44408 kgb-1 UniProt O44408 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707591 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707591 Reactome R-CEL-450355-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450355-2.1 jnk-1 MAPK9 Q8WQG9 Reactome DB_ID: 10707593 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707593 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707593 Reactome R-CEL-450355-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450355-3.1 Reactome Database ID Release 81 10707595 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707595 Reactome R-CEL-450355-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450355-4.1 Converted from EntitySet in Reactome Homologues of MAPK10 Reactome DB_ID: 10707603 kgb-2 MAPK10 H2KZI0 Reactome DB_ID: 10707597 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707597 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707597 Reactome R-CEL-450352 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450352.1 kgb-1 MAPK10 O44408 Reactome DB_ID: 10707599 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707599 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707599 Reactome R-CEL-450352-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450352-2.1 jnk-1 MAPK10 Q8WQG9 Reactome DB_ID: 10707601 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707601 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707601 Reactome R-CEL-450352-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450352-3.1 Reactome Database ID Release 81 10707603 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707603 Reactome R-CEL-450352-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450352-4.1 Reactome Database ID Release 81 10707605 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707605 Reactome R-CEL-450289 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450289.1 2 2 Converted from EntitySet in Reactome p-MAPK8,9,10 phosphorylated JNKs: MAPK8_MAPK9_MAPK10 Reactome DB_ID: 10707625 Q8WQG9 phospho-jnk-1 p-T,Y-MAPK8 Reactome DB_ID: 10707607 1 EQUAL 427 EQUAL Reactome Database ID Release 81 10707607 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707607 Reactome R-CEL-194371 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-194371.1 Converted from EntitySet in Reactome Homologues of p-T183,Y185-MAPK9 Reactome DB_ID: 10707615 H2KZI0 phospho-kgb-2 p-T183,Y185-MAPK9 Reactome DB_ID: 10707609 183 EQUAL 185 EQUAL 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707609 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707609 Reactome R-CEL-450293 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450293.1 O44408 phospho-kgb-1 p-T183,Y185-MAPK9 Reactome DB_ID: 10707611 183 EQUAL 185 EQUAL 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707611 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707611 Reactome R-CEL-450293-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450293-2.1 Q8WQG9 phospho-jnk-1 p-T183,Y185-MAPK9 Reactome DB_ID: 10707613 183 EQUAL 185 EQUAL 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707613 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707613 Reactome R-CEL-450293-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450293-3.1 Reactome Database ID Release 81 10707615 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707615 Reactome R-CEL-450293-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450293-4.1 Converted from EntitySet in Reactome Homologues of p-T221,Y223-MAPK10 Reactome DB_ID: 10707623 H2KZI0 phospho-kgb-2 p-T221,Y223-MAPK10 Reactome DB_ID: 10707617 221 EQUAL 223 EQUAL 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707617 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707617 Reactome R-CEL-450214 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450214.1 O44408 phospho-kgb-1 p-T221,Y223-MAPK10 Reactome DB_ID: 10707619 221 EQUAL 223 EQUAL 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707619 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707619 Reactome R-CEL-450214-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450214-2.1 Q8WQG9 phospho-jnk-1 p-T221,Y223-MAPK10 Reactome DB_ID: 10707621 221 EQUAL 223 EQUAL 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707621 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707621 Reactome R-CEL-450214-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450214-3.1 Reactome Database ID Release 81 10707623 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707623 Reactome R-CEL-450214-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450214-4.1 Reactome Database ID Release 81 10707625 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707625 Reactome R-CEL-450226 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450226.1 ACTIVATION Q20347 phospho-mkk-4 p-S257,T261-MAP2K4 Reactome DB_ID: 10707632 UniProt:Q20347 mkk-4 UniProt Q20347 257 EQUAL 261 EQUAL 1 EQUAL 399 EQUAL Reactome Database ID Release 81 10707632 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707632 Reactome R-CEL-168170 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168170.1 GENE ONTOLOGY GO:0008545 Reactome Database ID Release 81 10707633 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707633 Reactome Database ID Release 81 10707635 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707635 Reactome R-CEL-168162 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168162.1 Activated human JNK kinases (MKK4 and MKK7) phosphorylate Thr183 and Tyr185 residues in the characteristic Thr-Pro-Tyr phosphoacceptor loop of each JNK. <p>JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 cascade requires both MKK4 and MKK7. Some studies reported that in three JNK isoforms tested MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183). 16186825 Pubmed 2005 Essential function for the kinase TAK1 in innate and adaptive immune responses Sato, S Sanjo, H Takeda, K Ninomiya-Tsuji, J Yamamoto, M Kawai, T Matsumoto, K Takeuchi, O Akira, Shizuo Nat Immunol 6:1087-95 17875933 Pubmed 2007 Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death Wang, X Nadarajah, B Robinson, AC McColl, BW Jin, JW Dajas-Bailador, F Boot-Handford, RP Tournier, C Mol Cell Biol 27:7935-46 18713996 Pubmed 2008 Synoviocyte innate immune responses: I. Differential regulation of interferon responses and the JNK pathway by MAPK kinases Yoshizawa, T Hammaker, D Sweeney, SE Boyle, DL Firestein, GS J Immunol 181:3252-8 9162092 Pubmed 1997 Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo. Deacon, K Blank, JL J Biol Chem 272:14489-96 13130464 Pubmed 2003 Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK Sundarrajan, M Boyle, DL Chabaud-Riou, M Hammaker, D Firestein, GS Arthritis Rheum 48:2450-60 11062067 Pubmed 2000 Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7 Fleming, Y Armstrong, CG Morrice, N Paterson, A Goedert, M Cohen, P Biochem J 352:145-54 LEFT-TO-RIGHT Activated human JNKs migrate to nucleoplasm 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> Converted from EntitySet in Reactome p-MAPK8,9,10 Phosphorylated JNKs: MAPK8, MAPK9, MAPK10 Reactome DB_ID: 10707566 Q8WQG9 phospho-jnk-1 p-T,Y-MAPK8 Reactome DB_ID: 10707530 1 EQUAL 427 EQUAL Reactome Database ID Release 81 10707530 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707530 Reactome R-CEL-216349 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-216349.1 Converted from EntitySet in Reactome Homologues of p-T183,Y185-MAPK9 Reactome DB_ID: 10707550 H2KZI0 phospho-kgb-2 p-T183,Y185-MAPK9 Reactome DB_ID: 10707537 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707537 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707537 Reactome R-CEL-450319 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450319.1 O44408 phospho-kgb-1 p-T183,Y185-MAPK9 Reactome DB_ID: 10707544 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707544 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707544 Reactome R-CEL-450319-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450319-2.1 Q8WQG9 phospho-jnk-1 p-T183,Y185-MAPK9 Reactome DB_ID: 10707548 1 EQUAL 424 EQUAL Reactome Database ID Release 81 10707548 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707548 Reactome R-CEL-450319-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450319-3.1 Reactome Database ID Release 81 10707550 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707550 Reactome R-CEL-450319-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450319-4.1 Converted from EntitySet in Reactome Homologues of p-T221,Y223-MAPK10 Reactome DB_ID: 10707564 H2KZI0 phospho-kgb-2 p-T221,Y223-MAPK10 Reactome DB_ID: 10707554 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707554 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707554 Reactome R-CEL-450311 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450311.1 O44408 phospho-kgb-1 p-T221,Y223-MAPK10 Reactome DB_ID: 10707558 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707558 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707558 Reactome R-CEL-450311-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450311-2.1 Q8WQG9 phospho-jnk-1 p-T221,Y223-MAPK10 Reactome DB_ID: 10707562 1 EQUAL 464 EQUAL Reactome Database ID Release 81 10707562 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707562 Reactome R-CEL-450311-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450311-3.1 Reactome Database ID Release 81 10707564 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707564 Reactome R-CEL-450311-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450311-4.1 Reactome Database ID Release 81 10707566 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707566 Reactome R-CEL-450253 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450253.1 Reactome Database ID Release 81 10723952 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10723952 Reactome R-CEL-450348 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450348.1 c-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. 9195981 Pubmed 1997 A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion. Mizukami, Y Yoshioka, K Morimoto, S Yoshida, K J Biol Chem 272:16657-62 12193592 Pubmed 2002 Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the low density lipoprotein receptor-related protein (LRP) Lutz, C Nimpf, J Jenny, M Boecklinger, K Enzinger, C Utermann, G Baier-Bitterlich, G Baier, G J Biol Chem 277:43143-51 LEFT-TO-RIGHT 2.7.11 Activated JNKs phosphorylate c-JUN 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> 2 JUN jun-1 G5ECU7 Reactome DB_ID: 10707578 UniProt:G5ECU7 jun-1 UniProt G5ECU7 1 EQUAL 331 EQUAL Reactome Database ID Release 81 10707578 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707578 Reactome R-CEL-450250 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450250.1 2 G5ECU7 phospho-jun-1 p-S63,S73-JUN Reactome DB_ID: 10707582 63 EQUAL 73 EQUAL 1 EQUAL 331 EQUAL Reactome Database ID Release 81 10707582 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707582 Reactome R-CEL-450237 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-450237.1 ACTIVATION GENE ONTOLOGY GO:0004705 Reactome Database ID Release 81 10707583 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707583 Reactome Database ID Release 81 10707585 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10707585 Reactome R-CEL-168136 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-168136.1 JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus. 10871633 Pubmed 2000 c-Jun inhibits transforming growth factor beta-mediated transcription by repressing Smad3 transcriptional activity Dennler, S Prunier, C Ferrand, N Gauthier, JM Atfi, A J Biol Chem 275:28858-65 9561845 Pubmed 1998 Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development Ip, YT Davis, RJ Curr Opin Cell Biol 10:205-19 18793328 Pubmed 2008 c-Jun expression, activation and function in neural cell death, inflammation and repair Raivich, G J Neurochem 107:898-906 LEFT-TO-RIGHT KDM6B binds iron 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> Fe2+ iron (ferrous) Fe(II) Reactome DB_ID: 111793 iron(2+) [ChEBI:29033] iron(2+) FE (II) ION Fe2+ Fe(2+) iron ion(2+) Fe(II) Ferrous ion ChEBI CHEBI:29033 Reactome Database ID Release 81 111793 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111793 Reactome R-ALL-111793 4 Reactome stable identifier. Use this 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-111793.4 COMPOUND C00023 Converted from EntitySet in Reactome Homologues of KDM6B Reactome DB_ID: 10744068 utx-1 KDM6B A0A131MBT2 Reactome DB_ID: 10744051 UniProt:A0A131MBT2 utx-1 UniProt A0A131MBT2 1 EQUAL 1643 EQUAL Reactome Database ID Release 81 10744051 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10744051 Reactome R-CEL-1629833 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1629833.1 KDM6B jmjd-3.3 A0A131MD13 Reactome DB_ID: 10744056 UniProt:A0A131MD13 jmjd-3.3 UniProt A0A131MD13 1 EQUAL 1643 EQUAL Reactome Database ID Release 81 10744056 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10744056 Reactome R-CEL-1629833-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1629833-2.1 KDM6B jmjd-3.2 Q19760 Reactome DB_ID: 10744061 UniProt:Q19760 jmjd-3.2 UniProt Q19760 1 EQUAL 1643 EQUAL Reactome Database ID Release 81 10744061 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10744061 Reactome R-CEL-1629833-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1629833-3.1 KDM6B jmjd-3.1 Q95QK3 Reactome DB_ID: 10744066 UniProt:Q95QK3 jmjd-3.1 UniProt Q95QK3 1 EQUAL 1643 EQUAL Reactome Database ID Release 81 10744066 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10744066 Reactome R-CEL-1629833-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1629833-4.1 Reactome Database ID Release 81 10744068 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10744068 Reactome R-CEL-1629833-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-1629833-5.1 KDM6B:Fe2+ Reactome DB_ID: 10767694 1 1 Reactome Database ID Release 81 10767694 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10767694 Reactome R-CEL-3222589 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-3222589.1 Reactome Database ID Release 81 10767696 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10767696 Reactome R-CEL-8979071 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-8979071.1 KDM6B (JMJD3) binds iron. Formation of complex with Fe(II) is needed for the catalytic activity of KDM6B (De Santa et al. 2007). 17825402 Pubmed 2007 The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing De Santa, Francesca Totaro, Maria Grazia Prosperini, Elena Notarbartolo, Samuele Testa, Giuseppe Natoli, Gioacchino Cell 130:1083-94 Reactome Database ID Release 81 10772192 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10772192 Reactome R-CEL-2559580 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CEL-2559580.1 Oxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al. 2009) or independent of oncogenic signaling. Prolonged exposure to interferon-beta (IFNB, IFN-beta) also results in ROS increase (Moiseeva et al. 2006). ROS oxidize thioredoxin (TXN), which causes TXN to dissociate from the N-terminus of MAP3K5 (ASK1), enabling MAP3K5 to become catalytically active (Saitoh et al. 1998). ROS also stimulate expression of Ste20 family kinases MINK1 (MINK) and TNIK through an unknown mechanism, and MINK1 and TNIK positively regulate MAP3K5 activation (Nicke et al. 2005).<p> <br>MAP3K5 phosphorylates and activates MAP2K3 (MKK3) and MAP2K6 (MKK6) (Ichijo et al. 1997, Takekawa et al. 2005), which act as p38 MAPK kinases, as well as MAP2K4 (SEK1) (Ichijo et al. 1997, Matsuura et al. 2002), which, together with MAP2K7 (MKK7), acts as a JNK kinase.<p> <br>MKK3 and MKK6 phosphorylate and activate p38 MAPK alpha (MAPK14) and beta (MAPK11) (Raingeaud et al. 1996), enabling p38 MAPKs to phosphorylate and activate MAPKAPK2 (MK2) and MAPKAPK3 (MK3) (Ben-Levy et al. 1995, Clifton et al. 1996, McLaughlin et al. 1996, Sithanandam et al. 1996, Meng et al. 2002, Lukas et al. 2004, White et al. 2007), as well as MAPKAPK5 (PRAK) (New et al. 1998 and 2003, Sun et al. 2007).<p> <br>Phosphorylation of JNKs (MAPK8, MAPK9 and MAPK10) by MAP3K5-activated MAP2K4 (Deacon and Blank 1997, Fleming et al. 2000) allows JNKs to migrate to the nucleus (Mizukami et al. 1997) where they phosphorylate JUN. Phosphorylated JUN binds FOS phosphorylated by ERK1 or ERK2, downstream of activated RAS (Okazaki and Sagata 1995, Murphy et al. 2002), forming the activated protein 1 (AP-1) complex (FOS:JUN heterodimer) (Glover and Harrison 1995, Ainbinder et al. 1997). <p> <br>Activation of p38 MAPKs and JNKs downstream of MAP3K5 (ASK1) ultimately converges on transcriptional regulation of CDKN2A locus. In dividing cells, nucleosomes bound to the CDKN2A locus are trimethylated on lysine residue 28 of histone H3 (HIST1H3A) by the Polycomb repressor complex 2 (PRC2), creating the H3K27Me3 (Me3K-28-HIST1H3A) mark (Bracken et al. 2007, Kotake et al. 2007). The expression of Polycomb constituents of PRC2 (Kuzmichev et al. 2002) - EZH2, EED and SUZ12 - and thereby formation of the PRC2, is positively regulated in growing cells by E2F1, E2F2 and E2F3 (Weinmann et al. 2001, Bracken et al. 2003). H3K27Me3 mark serves as a docking site for the Polycomb repressor complex 1 (PRC1) that contains BMI1 (PCGF4) and is therefore named PRC1.4, leading to the repression of transcription of p16INK4A and p14ARF from the CDKN2A locus, where PCR1.4 mediated repression of p14ARF transcription in humans may be context dependent (Voncken et al. 2005, Dietrich et al. 2007, Agherbi et al. 2009, Gao et al. 2012). MAPKAPK2 and MAPKAPK3, activated downstream of the MAP3K5-p38 MAPK cascade, phosphorylate BMI1 of the PRC1.4 complex, leading to dissociation of PRC1.4 complex from the CDKN2A locus and upregulation of p14ARF transcription (Voncken et al. 2005). AP-1 transcription factor, formed as a result of MAP3K5-JNK signaling, as well as RAS signaling, binds the promoter of KDM6B (JMJD3) gene and stimulates KDM6B expression. KDM6B is a histone demethylase that removes H3K27Me3 mark i.e. demethylates lysine K28 of HIST1H3A, thereby preventing PRC1.4 binding to the CDKN2A locus and allowing transcription of p16INK4A (Agger et al. 2009, Barradas et al. 2009, Lin et al. 2012).<p> <br>p16INK4A inhibits phosphorylation-mediated inactivation of RB family members by CDK4 and CDK6, leading to cell cycle arrest (Serrano et al. 1993). p14ARF inhibits MDM2-mediated degradation of TP53 (p53) (Zhang et al. 1998), which also contributes to cell cycle arrest in cells undergoing oxidative stress. 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