BioPAX pathway converted from "Activated TAK1 mediates Jun kinases (JNK) phosphorylation and activation" in the Reactome database. Activated TAK1 mediates Jun kinases (JNK) phosphorylation and activation C-Jun NH2 terminal kinases are stress activated MAPKs, also known as 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.<p>Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7). Authored: Shamovsky, V, 2009-09-22 Reviewed: D'Eustachio, P, 2010-05-23 Edited: Shamovsky, V, 2011-02-17 LEFT-TO-RIGHT 2.7.11.1 Phosphorylation of MKK4 by activated TAK1 Phosphorylation of MKK4 and MKK7 by TAK1 occurs at the typical Ser-Xaa-Ala-Xaa-Thr motif in their activation loops. <p>Residues involved in activation of these protein kinases correspond to human Ser271, Thr275 in MKK7 and Ser257, Thr261 in MKK4.<p>Cell lines lacking MKK4 exhibit defective activation of JNK and AP-1 dependent transcription activity in response to some cellular stresses; JNK and p38 MAPK activities were decreased by around 80% and 20%, respectively, following the deletion of the mkk4 gene.<p>Chicken MKK4 protein as confirmed by mRNA sequence shows 96% identity to human MKK4 (UniProtKB sequence data using NCBI BLASTP 2.2.20). Multiple sequence alignment of the proteins by ClustalW demonstrated that chicken MKK4 serine residue 224 and threonine 228 correspond to human Ser257 and Thr261, that are required for the activation.<p> Since no MKK7 ortholog was identified in the chicken genome, only chicken MKK4 protein is annotated in the chicken JNK pathway as a homolog of the well characterized human MKK4 / MKK7 proteins. Authored: Shamovsky, V, 2009-09-22 Reviewed: D'Eustachio, P, 2010-05-23 Edited: Shamovsky, V, 2010-05-04 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 cytosol GENE ONTOLOGY GO:0005829 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 82 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 Reactome http://www.reactome.org COMPOUND C00002 additional information MI MI:0361 2 MKK4 MAP2K4 SEK1 C-JUN N-terminal kinase kinase 1 Reactome DB_ID: 437642 ENSEMBL:ENSGALP00000001475 MKK4 MKK4 MAP2K4 Gallus gallus NCBI Taxonomy 9031 ENSEMBL ENSGALP00000001475 Reactome Database ID Release 82 437642 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=437642 Reactome R-GGA-437642 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-GGA-437642.1 phosphorylated MKK4 Reactome DB_ID: 437975 O-phospho-L-serine MOD MOD:00046 O-phospho-L-threonine MOD MOD:00047 Reactome Database ID Release 82 437975 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=437975 Reactome R-GGA-437975 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-GGA-437975.1 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 82 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 activeUnit: #Protein15 Converted from EntitySet in Reactome Activated chicken TAK1 complexes Reactome DB_ID: 975491 pUB-TRAF6:TAB2:TAB3:TAB1:free K63-pUb chain:phospho TAK1 Reactome DB_ID: 921146 pUb_TRAF6 Reactome DB_ID: 451455 K63_polyubiquitin chain Reactome DB_ID: 434061 Reactome Database ID Release 82 434061 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=434061 Reactome R-GGA-434061 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-GGA-434061.1 1 TRAF6 Reactome DB_ID: 433886 UniProt:E1C626 TRAF6 TRAF6 SIMILARITY: Contains 1 MATH domain. UniProt E1C626 Reactome Database ID Release 82 433886 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=433886 Reactome R-GGA-433886 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-GGA-433886.1 1 Reactome Database ID Release 82 451455 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=451455 Reactome R-GGA-451455 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-GGA-451455.1 2 TAB2 Reactome DB_ID: 434032 ENSEMBL:ENSGALP00000020155 TAB2 TAB2 MAP3K7IP2 (TAB2) ENSEMBL ENSGALP00000020155 1 EQUAL 697 EQUAL Reactome Database ID Release 82 434032 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=434032 Reactome R-GGA-434032 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-GGA-434032.1 2 2 TAB1 Reactome DB_ID: 433882 UniProt:Q5ZJW3 RCJMB04_15c17 RCJMB04_15c17 <submittedName> <fullName>Putative uncharacterized protein</fullName> </submittedName> UniProt Q5ZJW3 1 EQUAL 438 EQUAL Reactome Database ID Release 82 433882 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=433882 Reactome R-GGA-433882 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-GGA-433882.1 2 phosphorylated TAK1 Reactome DB_ID: 451473 ENSEMBL:ENSGALP00000025101 TGF-beta- activated kinase 1 TGF-beta- activated kinase 1 MAP3K7 ENSEMBL ENSGALP00000025101 1 EQUAL 617 EQUAL Reactome Database ID Release 82 451473 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=451473 Reactome R-GGA-451473 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-GGA-451473.1 2 TAB3 Reactome DB_ID: 442867 ENSEMBL:ENSGALP00000026205 TAB3 TAB3 MAP3K7IP3 ENSEMBL ENSGALP00000026205 Reactome Database ID Release 82 442867 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=442867 Reactome R-GGA-442867 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-GGA-442867.1 2 Reactome Database ID Release 82 921146 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=921146 Reactome R-GGA-921146 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-GGA-921146.1 p-IRAK2: pUb_oligo TRAF6 : phospho TAK1 :TAB1 : TAB2/TAB3 : K63linked free pUb chain Reactome DB_ID: 451458 plasma membrane GENE ONTOLOGY GO:0005886 free K63_polyubiquitin chain Reactome DB_ID: 451962 Reactome Database ID Release 82 451962 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=451962 Reactome R-GGA-451962 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-GGA-451962.1 2 phosphorylated TAK1 Reactome DB_ID: 975700 1 EQUAL 617 EQUAL Reactome Database ID Release 82 975700 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=975700 Reactome R-GGA-975700 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-GGA-975700.1 2 pUb oligo TRAF6 : p-IRAK2 Reactome DB_ID: 451453 phosphorylated IRAK2 Reactome DB_ID: 433788 UniProt:Q5F382 RCJMB04_29d24 RCJMB04_29d24 <submittedName> <fullName>Putative uncharacterized protein</fullName> </submittedName> UniProt Q5F382 phosphorylated residue MOD MOD:00696 1 EQUAL 691 EQUAL Reactome Database ID Release 82 433788 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=433788 Reactome R-GGA-433788 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-GGA-433788.1 1 K63 linked pUb TRAF6 Reactome DB_ID: 433856 K63-linked Ub TRAF6 Reactome DB_ID: 975686 ubiquitinylated lysine MOD MOD:01148 Reactome Database ID Release 82 975686 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=975686 Reactome R-GGA-975686 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-GGA-975686.1 1 K63 polyubiquitin chain Reactome DB_ID: 975690 Reactome Database ID Release 82 975690 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=975690 Reactome R-GGA-975690 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-GGA-975690.1 1 Reactome Database ID Release 82 433856 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=433856 Reactome R-GGA-433856 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-GGA-433856.1 3 Reactome Database ID Release 82 451453 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=451453 Reactome R-GGA-451453 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-GGA-451453.1 1 TAB1 Reactome DB_ID: 975709 1 EQUAL 438 EQUAL Reactome Database ID Release 82 975709 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=975709 Reactome R-GGA-975709 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-GGA-975709.1 2 Converted from EntitySet in Reactome chicken TAB2/TAB3 Reactome DB_ID: 975702 TAB2 Reactome DB_ID: 975705 1 EQUAL 697 EQUAL Reactome Database ID Release 82 975705 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=975705 Reactome R-GGA-975705 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-GGA-975705.1 TAB3 Reactome DB_ID: 975707 Reactome Database ID Release 82 975707 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=975707 Reactome R-GGA-975707 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-GGA-975707.1 Reactome Database ID Release 82 975702 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=975702 Reactome R-GGA-975702 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-GGA-975702.1 2 Reactome Database ID Release 82 451458 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=451458 Reactome R-GGA-451458 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-GGA-451458.1 Reactome Database ID Release 82 975491 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=975491 Reactome R-GGA-975491 2 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-GGA-975491.2 GENE ONTOLOGY GO:0004674 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 82 434076 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=434076 phosphorylated TAK1 Reactome DB_ID: 433952 endosome membrane GENE ONTOLOGY GO:0010008 1 EQUAL 617 EQUAL Reactome Database ID Release 82 433952 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=433952 Reactome R-GGA-433952 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-GGA-433952.1 Reactome Database ID Release 82 437999 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=437999 Reactome R-GGA-437999 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-GGA-437999.1 15837794 Pubmed 2005 Simultaneous 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 genes Thiefes, A Wolter, S Mushinski, JF Hoffmann, E Dittrich-Breiholz, O Graue, N Dörrie, A Schneider, H Wirth, D Luckow, B Resch, K Kracht, M J Biol Chem 280:27728-41 8533096 Pubmed 1995 Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction Yamaguchi, K Shirakabe, K Shibuya, H Irie, K Oishi, I Ueno, N Taniguchi, T Nishida, E Matsumoto, K Science 270:2008-11 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 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 LEFT-TO-RIGHT 2.7.12.1 MKK4 phosphorylates JNK Activated JNK kinases (MKK4 and MKK7) phosphorylate threonine and tyrosine residues in the characteristic Thr-Pro-Tyr phosphoacceptor loop of each JNK isoform.<p>Chicken JNK2(MAPK9) shows 98% identity with human JNK2 (UniProtKB sequence data using NCBI BLASTP 2.2.20). Multiple sequence alignment of the human, mouse and chicken JNK2 proteins by ClustalW showed that Thr183 and Tyr185 residues, that are responsible for the JNK activation in human, are identical for all three orthologs.<p>Other chicken JNK isoforms JNK1(MAPK8) and JNK3(MAPK10), whose existence is confirmed at the transcript level, share 99% and 95% amino-acid sequence identity with their human counterparts respectively. Authored: Shamovsky, V, 2009-09-22 Reviewed: D'Eustachio, P, 2010-05-23 Edited: Shamovsky, V, 2011-02-17 2 Converted from EntitySet in Reactome JNK homologs Reactome DB_ID: 433872 MAPK9_(JNK2) mitogen-activated protein kinase 9 Reactome DB_ID: 434057 UniProt:P79996 MAPK9 MAPK9 JNK2 FUNCTION Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (By similarity). May play a role in the development of the central nervous system during embryogenesis. May play a role in the regulation of the circadian clock (By similarity).ACTIVITY REGULATION Activated by threonine and tyrosine phosphorylation.TISSUE SPECIFICITY Expressed in the neuroepithelium of developing brain at stages 16 to 26.DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.PTM Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. UniProt P79996 1 EQUAL 382 EQUAL Reactome Database ID Release 82 434057 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=434057 Reactome R-GGA-434057 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-GGA-434057.1 MAPK10 Reactome DB_ID: 433946 ENSEMBL:ENSGALP00000018075 MAPK10 MAPK10 ENSEMBL ENSGALP00000018075 Reactome Database ID Release 82 433946 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=433946 Reactome R-GGA-433946 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-GGA-433946.1 MAPK8 Reactome DB_ID: 433810 ENSEMBL:ENSGALP00000009848 MAPK8 MAPK8 ENSEMBL ENSGALP00000009848 1 EQUAL 427 EQUAL Reactome Database ID Release 82 433810 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=433810 Reactome R-GGA-433810 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-GGA-433810.1 Reactome Database ID Release 82 433872 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=433872 Reactome R-GGA-433872 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-GGA-433872.1 Converted from EntitySet in Reactome phosphorylated JNK homologs Reactome DB_ID: 437957 phosphorylated MAPK9_(JNK2) mitogen-activated protein kinase 9 Reactome DB_ID: 438015 183 EQUAL 185 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 1 EQUAL 382 EQUAL Reactome Database ID Release 82 438015 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=438015 Reactome R-GGA-438015 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-GGA-438015.1 phosphorylated MAPK10 Reactome DB_ID: 437973 Reactome Database ID Release 82 437973 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=437973 Reactome R-GGA-437973 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-GGA-437973.1 phosphorylated MAPK8 Reactome DB_ID: 437976 1 EQUAL 427 EQUAL Reactome Database ID Release 82 437976 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=437976 Reactome R-GGA-437976 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-GGA-437976.1 Reactome Database ID Release 82 437957 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=437957 Reactome R-GGA-437957 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-GGA-437957.1 2 ACTIVATION activeUnit: #Protein2 GENE ONTOLOGY GO:0004712 Reactome Database ID Release 82 438025 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=438025 Reactome Database ID Release 82 438005 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=438005 Reactome R-GGA-438005 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-GGA-438005.1 LEFT-TO-RIGHT Activated JNK migrates to the nucleoplasm Shortly after phosphorylation JNKs are translocated to nucleus where they associate and activate their target transcription factors. Authored: Shamovsky, V, 2009-09-22 Reviewed: D'Eustachio, P, 2010-05-23 Edited: Shamovsky, V, 2010-05-04 Converted from EntitySet in Reactome phosphorylated JNK homologs Reactome DB_ID: 438012 phosphorylated MAPK9_(JNK2) mitogen-activated protein kinase 9 Reactome DB_ID: 437993 nucleoplasm GENE ONTOLOGY GO:0005654 1 EQUAL 382 EQUAL Reactome Database ID Release 82 437993 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=437993 Reactome R-GGA-437993 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-GGA-437993.1 phosphorylated MAPK10 Reactome DB_ID: 437960 Reactome Database ID Release 82 437960 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=437960 Reactome R-GGA-437960 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-GGA-437960.1 phosphorylated MAPK8 Reactome DB_ID: 437983 1 EQUAL 427 EQUAL Reactome Database ID Release 82 437983 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=437983 Reactome R-GGA-437983 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-GGA-437983.1 Reactome Database ID Release 82 438012 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=438012 Reactome R-GGA-438012 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-GGA-438012.1 Reactome Database ID Release 82 437995 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=437995 Reactome R-GGA-437995 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-GGA-437995.1 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 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 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 Activation and dimerization of c-JUN in the nucleus Shortly after phosphorylation JNKs are translocated to nucleus where they associate and activate their target transcription factors. Authored: Shamovsky, V, 2009-09-22 Reviewed: D'Eustachio, P, 2010-05-23 Edited: Shamovsky, V, 2010-05-04 c-JUN Transcription factor AP-1 Reactome DB_ID: 438016 UniProt:P18870 JUN JUN FUNCTION Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. May be involved in activated KRAS-mediated transcriptional activation of USP28. May bind to the USP28 promoter.SUBUNIT Interacts with FOS to form a dimer. Interacts with Gallid herpesvirus 2 MEQ protein.SIMILARITY Belongs to the bZIP family. Jun subfamily. UniProt P18870 1 EQUAL 314 EQUAL Reactome Database ID Release 82 438016 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=438016 Reactome R-GGA-438016 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-GGA-438016.1 2 ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 29358 Reactome Database ID Release 82 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 4 activated c-JUN dimer Reactome DB_ID: 437991 phosphorylated c-JUN Transcription factor AP-1 Reactome DB_ID: 438013 63 EQUAL 73 EQUAL 1 EQUAL 314 EQUAL Reactome Database ID Release 82 438013 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=438013 Reactome R-GGA-438013 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-GGA-438013.1 2 Reactome Database ID Release 82 437991 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=437991 Reactome R-GGA-437991 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-GGA-437991.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 113582 Reactome Database ID Release 82 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 4 ACTIVATION activeUnit: #Protein22 activeUnit: #Protein23 activeUnit: #Protein21 GENE ONTOLOGY GO:0004705 Reactome Database ID Release 82 438001 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=438001 Reactome Database ID Release 82 438026 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=438026 Reactome R-GGA-438026 2 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-GGA-438026.2 18793328 Pubmed 2008 c-Jun expression, activation and function in neural cell death, inflammation and repair Raivich, G J Neurochem 107:898-906 INHIBITION Reactome Database ID Release 82 442857 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=442857 Reactome R-GGA-442857 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-GGA-442857.1 Converted from EntitySet in Reactome MAPK phosphatases dual specificity phosphatases Reactome DB_ID: 442886 MKP1 Dual specificity protein phosphatase 1 Reactome DB_ID: 442888 UniProt:O42253 Dual specificity protein phosphatase 1 Dual specificity protein phosphatase 1 MKP1 UniProt O42253 1 EQUAL 353 EQUAL Reactome Database ID Release 82 442888 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=442888 Reactome R-GGA-442888 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-GGA-442888.1 MKP2 DUSP4 Reactome DB_ID: 442850 UniProt:Q9PW71 DUSP4 DUSP4 MKP2 FUNCTION Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.SIMILARITY Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. UniProt Q9PW71 1 EQUAL 375 EQUAL Reactome Database ID Release 82 442850 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=442850 Reactome R-GGA-442850 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-GGA-442850.1 MKP3 DUSP6 Reactome DB_ID: 442887 UniProt:Q7T2L9 MKP3 MKP3 dual specificity phosphatase 6 UniProt Q7T2L9 1 EQUAL 382 EQUAL Reactome Database ID Release 82 442887 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=442887 Reactome R-GGA-442887 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-GGA-442887.1 MKP5 DUSP10 Reactome DB_ID: 442877 UniProt:Q5ZJF8 Dual specificity protein phosphatase 10 Dual specificity protein phosphatase 10 RCJMB04_18i8 UniProt Q5ZJF8 1 EQUAL 478 EQUAL Reactome Database ID Release 82 442877 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=442877 Reactome R-GGA-442877 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-GGA-442877.1 DUSP16 Reactome DB_ID: 442935 ENSEMBL:ENSGALP00000001453 DUSP16 DUSP16 ENSEMBL ENSGALP00000001453 Reactome Database ID Release 82 442935 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=442935 Reactome R-GGA-442935 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-GGA-442935.1 DUSP3 dual specificity phosphatase 3 Reactome DB_ID: 442882 ENSEMBL:ENSGALP00000016127 DUSP3 DUSP3 ENSEMBL ENSGALP00000016127 Reactome Database ID Release 82 442882 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=442882 Reactome R-GGA-442882 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-GGA-442882.1 DUSP5 Reactome DB_ID: 442941 ENSEMBL:ENSGALP00000013956 dual specificity phosphatase 5 dual specificity phosphatase 5 DUSP5 ENSEMBL ENSGALP00000013956 Reactome Database ID Release 82 442941 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=442941 Reactome R-GGA-442941 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-GGA-442941.1 DUSP8 Reactome DB_ID: 442917 ENSEMBL:ENSGALP00000010737 DUSP8 DUSP8 ENSEMBL ENSGALP00000010737 Reactome Database ID Release 82 442917 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=442917 Reactome R-GGA-442917 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-GGA-442917.1 MKP6 DUSP14 Reactome DB_ID: 442874 ENSEMBL:ENSGALP00000008741 DUSP14 DUSP14 dual specificity phosphatase 14 ENSEMBL ENSGALP00000008741 Reactome Database ID Release 82 442874 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=442874 Reactome R-GGA-442874 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-GGA-442874.1 Reactome Database ID Release 82 442886 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=442886 Reactome R-GGA-442886 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-GGA-442886.1 Reactome Database ID Release 82 437986 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=437986 Reactome R-GGA-437986 2 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-GGA-437986.2 7839144 Pubmed 1995 Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms Derijard, B Raingeaud, J Barrett, T Wu, IH Han, J Ulevitch, RJ Davis, RJ Science 267:682-5 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 11057897 Pubmed 2000 Signal transduction by the JNK group of MAP kinases Davis, RJ Cell 103:239-52 12471242 Pubmed 2002 Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases Johnson, GL Lapadat, R Science 298:1911-2 11460167 Pubmed 2001 TAK1 is a ubiquitin-dependent kinase of MKK and IKK Wang, C Deng, L Hong, M Akkaraju, GR Inoue, J Chen, ZJ Nature 412:346-51 GENE ONTOLOGY GO:0007254 gene ontology term for cellular process MI MI:0359