KEGG   PATHWAY: umr04630
Entry
umr04630                    Pathway                                
Name
JAK-STAT signaling pathway - Ursus maritimus (polar bear)
Description
The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeostasis in animals, from humans to flies. In mammals, the JAK/STAT pathway is the principal signaling mechanism for a wide array of cytokines and growth factors. Following the binding of cytokines to their cognate receptor, STATs are activated by members of the JAK family of tyrosine kinases. Once activated, they dimerize and translocate to the nucleus and modulate the expression of target genes. In addition to the activation of STATs, JAKs mediate the recruitment of other molecules such as the MAP kinases, PI3 kinase etc. These molecules process downstream signals via the Ras-Raf-MAP kinase and PI3 kinase pathways which results in the activation of additional transcription factors.
Class
Environmental Information Processing; Signal transduction
Pathway map
umr04630  JAK-STAT signaling pathway
umr04630

Other DBs
GO: 0007259
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103661804  IL2; interleukin-2 [KO:K05429]
103663832  IL4; interleukin-4 [KO:K05430]
103661362  IL7; interleukin-7 [KO:K05431]
103663953  IL9; interleukin-9 [KO:K05432]
103657977  IL15; interleukin-15 isoform X1 [KO:K05433]
103661805  IL21; interleukin-21 [KO:K05434]
103675809  thymic stromal lymphopoietin [KO:K05436]
103676245  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
103676409  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
103682591  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
103657902  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
103664716  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
103676865  LOW QUALITY PROTEIN: interleukin-9 receptor-like [KO:K05073]
103668438  IL9R; interleukin-9 receptor isoform X1 [KO:K05073]
103676282  IL15RA; LOW QUALITY PROTEIN: interleukin-15 receptor subunit alpha [KO:K05074]
103657903  IL21R; interleukin-21 receptor [KO:K05075]
103666288  CRLF2; cytokine receptor-like factor 2 [KO:K05078]
103670504  interleukin-3 [KO:K04736]
103663836  IL5; interleukin-5 [KO:K05428]
103670505  CSF2; granulocyte-macrophage colony-stimulating factor isoform X1 [KO:K05427]
103666330  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
103674266  IL5RA; interleukin-5 receptor subunit alpha isoform X1 [KO:K05067]
103666290  CSF2RA; granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
103666329  granulocyte-macrophage colony-stimulating factor receptor subunit alpha-like [KO:K05066]
103676415  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
103658871  IL6; interleukin-6 [KO:K05405]
103680260  IL11; interleukin-11 [KO:K05417]
103663833  IL13; LOW QUALITY PROTEIN: interleukin-13 [KO:K05435]
103657820  IL27; interleukin-27 subunit alpha [KO:K22629]
103661231  IL31; interleukin-31 [KO:K22631]
103681110  OSM; oncostatin-M isoform X1 [KO:K05418]
103681125  LIF; leukemia inhibitory factor [KO:K05419]
103666137  CNTF; ciliary neurotrophic factor [KO:K05420]
121103759  LOW QUALITY PROTEIN: cardiotrophin-1-like [KO:K05422]
103657877  cardiotrophin-2 [KO:K24382]
103679513  CLCF1; cardiotrophin-like cytokine factor 1 isoform X1 [KO:K05421]
103668717  IL6R; interleukin-6 receptor subunit alpha isoform X1 [KO:K05055]
103663669  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
103667059  IL11RA; interleukin-11 receptor subunit alpha isoform X1 [KO:K05056]
103677732  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X1 [KO:K05076]
103679731  IL13RA2; interleukin-13 receptor subunit alpha-2 [KO:K05077]
103682129  IL27RA; interleukin-27 receptor subunit alpha [KO:K19598]
103663670  IL31RA; interleukin-31 receptor subunit alpha [KO:K22630]
103664690  OSMR; oncostatin-M-specific receptor subunit beta isoform X1 [KO:K05057]
103664694  LIFR; leukemia inhibitory factor receptor [KO:K05058]
103667051  CNTFR; ciliary neurotrophic factor receptor subunit alpha isoform X1 [KO:K05059]
103657674  IL10; interleukin-10 [KO:K05443]
103657672  IL19; interleukin-19 [KO:K05444]
103656860  IL22; interleukin-22 [KO:K05445]
103657755  IL20; interleukin-20 isoform X1 [KO:K22667]
103657671  IL24; interleukin-24 [KO:K22668]
103656859  IL26; interleukin-26 [KO:K05446]
103662345  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
121099743  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
103663373  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
103678770  IL20RB; interleukin-20 receptor subunit beta [KO:K05137]
103666549  IL22RA1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
103663371  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
103681335  IL12A; interleukin-12 subunit alpha [KO:K05406]
103664531  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
103656219  IL23A; interleukin-23 subunit alpha [KO:K05426]
103674947  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
103663034  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
103663036  IL23R; interleukin-23 receptor [KO:K05065]
103670120  EPO; LOW QUALITY PROTEIN: erythropoietin [KO:K05437]
103665901  somatotropin [KO:K05438]
103678373  PRL; prolactin [KO:K05439]
103676077  THPO; thrombopoietin isoform X1 [KO:K06854]
103661676  CSF3; granulocyte colony-stimulating factor [KO:K05423]
103676631  leptin isoform X1 [KO:K05424]
103678709  EPOR; erythropoietin receptor isoform X1 [KO:K05079]
103664663  GHR; growth hormone receptor isoform X1 [KO:K05080]
103664719  PRLR; prolactin receptor [KO:K05081]
103670908  MPL; thrombopoietin receptor isoform X1 [KO:K05082]
103666378  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
103663045  LEPR; leptin receptor isoform X1 [KO:K05062]
103662147  interferon alpha-1/2-like [KO:K05414]
103662148  interferon alpha-1/2-like [KO:K05414]
103662149  interferon alpha-2-like [KO:K05414]
103680385  interferon alpha-1/2-like [KO:K05414]
103680386  interferon alpha-1/2-like [KO:K05414]
103666985  interferon alpha-1/2-like [KO:K05414]
121103043  interferon alpha-1/2-like [KO:K05414]
103662150  IFNB1; interferon beta [KO:K05415]
103666986  IFNE; interferon epsilon [KO:K05442]
103667005  IFNK; interferon kappa [KO:K05441]
103661020  LOW QUALITY PROTEIN: interferon lambda-1 [KO:K05447]
103661082  interferon lambda-3 [KO:K22669]
103673220  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
103673110  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
103666548  IFNLR1; interferon lambda receptor 1 [KO:K05140]
103656858  IFNG; interferon gamma [KO:K04687]
103663370  IFNGR1; interferon gamma receptor 1 [KO:K05132]
103673221  IFNGR2; interferon gamma receptor 2 [KO:K05133]
103661742  EGF; pro-epidermal growth factor isoform X2 [KO:K04357]
103670054  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
103676520  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
103674660  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103672737  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
103664600  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
103663059  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103663212  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
103675167  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
103678725  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
103659933  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
103656206  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
103672573  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103659686  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
103672571  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
103672570  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
103656427  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
103679279  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
103675084  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
121103675  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
103660099  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
103665967  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103673077  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
103671233  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
103661175  SOCS7; suppressor of cytokine signaling 7 [KO:K04699]
103658406  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
103676164  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
103667602  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
103674345  BCL2L1; bcl-2-like protein 1 isoform X2 [KO:K04570]
103665531  serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
103661697  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103671139  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103675743  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103664092  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
103665536  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103659730  aldehyde oxidase [KO:K00157] [EC:1.2.3.1]
103659731  aldehyde oxidase 4-like [KO:K00157] [EC:1.2.3.1]
103659946  aldehyde oxidase 2 [KO:K00157] [EC:1.2.3.1]
103665875  LOW QUALITY PROTEIN: glial fibrillary acidic protein [KO:K05640]
103659467  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
103664209  STAM; signal transducing adapter molecule 1 [KO:K04705]
103673356  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
103656221  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
103668810  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
103674159  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103679050  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
103663831  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X3 [KO:K16063] [EC:2.3.2.-]
103678403  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X1 [KO:K16064] [EC:2.3.2.-]
103681832  PIAS4; E3 SUMO-protein ligase PIAS4 isoform X1 [KO:K16065] [EC:2.3.2.27]
103672852  LOW QUALITY PROTEIN: four and a half LIM domains protein 1 [KO:K14365]
121102270  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
103661289  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
103682087  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103671891  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103665409  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103669173  LOW QUALITY PROTEIN: GTPase HRas-like [KO:K02833]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103666660  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
Reference
PMID:22383755
  Authors
Harrison DA
  Title
The Jak/STAT pathway.
  Journal
Cold Spring Harb Perspect Biol 4:a011205 (2012)
DOI:10.1101/cshperspect.a011205
Reference
PMID:22339650
  Authors
Kiu H, Nicholson SE
  Title
Biology and significance of the JAK/STAT signalling pathways.
  Journal
Growth Factors 30:88-106 (2012)
DOI:10.3109/08977194.2012.660936
Reference
PMID:21372217
  Authors
Hervas-Stubbs S, Perez-Gracia JL, Rouzaut A, Sanmamed MF, Le Bon A, Melero I
  Title
Direct effects of type I interferons on cells of the immune system.
  Journal
Clin Cancer Res 17:2619-27 (2011)
DOI:10.1158/1078-0432.CCR-10-1114
Reference
PMID:25217450
  Authors
Fish EN, Platanias LC
  Title
Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes.
  Journal
Mol Cancer Res 12:1691-703 (2014)
DOI:10.1158/1541-7786.MCR-14-0450
Reference
PMID:21034406
  Authors
Ivanenkov YA, Balakin KV, Lavrovsky Y
  Title
Small molecule inhibitors of NF-kB and JAK/STAT signal transduction pathways as promising anti-inflammatory therapeutics.
  Journal
Mini Rev Med Chem 11:55-78 (2011)
DOI:10.2174/138955711793564079
Reference
PMID:25587654
  Authors
O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A
  Title
The JAK-STAT pathway: impact on human disease and therapeutic intervention.
  Journal
Annu Rev Med 66:311-28 (2015)
DOI:10.1146/annurev-med-051113-024537
Reference
PMID:24069565
  Authors
Zoranovic T, Grmai L, Bach EA
  Title
Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway.
  Journal
JAKSTAT 2:e25408 (2013)
DOI:10.4161/jkst.25408
Reference
PMID:16204702
  Authors
Ungureanu D, Silvennoinen O
  Title
SLIM trims STATs: ubiquitin E3 ligases provide insights for specificity in the regulation of cytokine signaling.
  Journal
Sci STKE 2005:pe49 (2005)
DOI:10.1126/stke.3042005pe49
Reference
PMID:23735217
  Authors
Richard AJ, Stephens JM
  Title
The role of JAK-STAT signaling in adipose tissue function.
  Journal
Biochim Biophys Acta 1842:431-9 (2014)
DOI:10.1016/j.bbadis.2013.05.030
Reference
PMID:24606160
  Authors
Sun Y, Lehmbecker A, Kalkuhl A, Deschl U, Sun W, Rohn K, Tzvetanova ID, Nave KA, Baumgartner W, Ulrich R
  Title
STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler's murine encephalomyelitis.
  Journal
Neuropathol Appl Neurobiol 41:347-70 (2015)
DOI:10.1111/nan.12133
Reference
PMID:10851053
  Authors
Hirano T, Ishihara K, Hibi M
  Title
Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
  Journal
Oncogene 19:2548-56 (2000)
DOI:10.1038/sj.onc.1203551
Reference
PMID:11114747
  Authors
Rane SG, Reddy EP
  Title
Janus kinases: components of multiple signaling pathways.
  Journal
Oncogene 19:5662-79 (2000)
DOI:10.1038/sj.onc.1203925
Reference
PMID:8682149
  Authors
Heim MH
  Title
The Jak-STAT pathway: specific signal transduction from the cell membrane to the nucleus.
  Journal
Eur J Clin Invest 26:1-12 (1996)
DOI:10.1046/j.1365-2362.1996.103248.x
Reference
PMID:30267440
  Authors
Morris R, Kershaw NJ, Babon JJ
  Title
The molecular details of cytokine signaling via the JAK/STAT pathway.
  Journal
Protein Sci 27:1984-2009 (2018)
DOI:10.1002/pro.3519
Reference
PMID:34492272
  Authors
Tzeng HT, Chyuan IT, Lai JH
  Title
Targeting the JAK-STAT pathway in autoimmune diseases and cancers: A focus on molecular mechanisms and therapeutic potential.
  Journal
Biochem Pharmacol 193:114760 (2021)
DOI:10.1016/j.bcp.2021.114760
Reference
PMID:32203403
  Authors
Salas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S, Vetrano S, Vande Casteele N
  Title
JAK-STAT pathway targeting for the treatment of inflammatory bowel disease.
  Journal
Nat Rev Gastroenterol Hepatol 17:323-337 (2020)
DOI:10.1038/s41575-020-0273-0
Related
pathway
umr04010  MAPK signaling pathway
umr04060  Cytokine-cytokine receptor interaction
umr04110  Cell cycle
umr04120  Ubiquitin mediated proteolysis
umr04151  PI3K-Akt signaling pathway
umr04210  Apoptosis
KO pathway
ko04630   
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