KEGG   PATHWAY: uar04630
Entry
uar04630                    Pathway                                
Name
JAK-STAT signaling pathway - Ursus americanus (American black 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
uar04630  JAK-STAT signaling pathway
uar04630

Other DBs
GO: 0007259
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123775506  HRAS; GTPase HRas isoform X1 [KO:K02833]
123775939  [KO:K05447]
123776417  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
123777305  EPO; LOW QUALITY PROTEIN: erythropoietin [KO:K05437]
123777576  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
123777751  EPOR; erythropoietin receptor isoform X1 [KO:K05079]
123778065  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
123778070  IL21R; interleukin-21 receptor [KO:K05075]
123778441  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
123778462  CLCF1; cardiotrophin-like cytokine factor 1 [KO:K05421]
123778529  IL31; interleukin-31 [KO:K22631]
123778683  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X1 [KO:K16064] [EC:2.3.2.-]
123778834  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
123778956  THPO; thrombopoietin isoform X1 [KO:K06854]
123779078  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123779112  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123779180  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123779321  [KO:K05436]
123779575  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123779817  IL12RB1; LOW QUALITY PROTEIN: interleukin-12 receptor subunit beta-1 [KO:K05063]
123779926  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
123779986  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
123780665  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
123780776  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
123780802  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
123780861  IL2RB; LOW QUALITY PROTEIN: interleukin-2 receptor subunit beta [KO:K05069]
123780918  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
123781019  IFNE; interferon epsilon [KO:K05442]
123781031  IFNB1; interferon beta [KO:K05415]
123781096  IL11RA; interleukin-11 receptor subunit alpha isoform X1 [KO:K05056]
123781124  IFNK; interferon kappa [KO:K05441]
123781241  [KO:K05414]
123781249  [KO:K05414]
123781251  [KO:K05414]
123781252  [KO:K05414]
123781255  [KO:K05414]
123781256  [KO:K05414]
123781260  [KO:K05414]
123781274  CNTFR; ciliary neurotrophic factor receptor subunit alpha isoform X1 [KO:K05059]
123781283  [KO:K05414]
123781329  [KO:K05414]
123781556  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
123781570  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123781804  CSF3; granulocyte colony-stimulating factor [KO:K05423]
123781848  [KO:K11223]
123781849  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
123781851  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
123782048  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
123782295  IL22RA1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
123782335  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
123782441  IFNLR1; interferon lambda receptor 1 [KO:K05140]
123783236  IL6R; interleukin-6 receptor subunit alpha isoform X1 [KO:K05055]
123783521  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
123783569  [KO:K05073]
123783593  [KO:K04498] [EC:2.3.1.48]
123784096  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123784206  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
123784207  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
123784593  IL27; interleukin-27 subunit alpha [KO:K22629]
123784664  CTF1; cardiotrophin-1 [KO:K05422]
123784769  [KO:K24382]
123784827  PIM1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
123784995  [KO:K05447]
123785070  CNTF; ciliary neurotrophic factor [KO:K05420]
123785469  PRLR; prolactin receptor isoform X1 [KO:K05081]
123785472  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
123785495  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
123785499  OSMR; oncostatin-M-specific receptor subunit beta isoform X1 [KO:K05057]
123785520  GHR; growth hormone receptor isoform X1 [KO:K05080]
123785653  IL24; interleukin-24 [KO:K22668]
123785705  STAM; signal transducing adapter molecule 1 [KO:K04705]
123785865  IL10; interleukin-10 [KO:K05443]
123785866  IL19; interleukin-19 [KO:K05444]
123785867  IL20; interleukin-20 isoform X1 [KO:K22667]
123785901  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
123786270  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123786407  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123786941  IL11; interleukin-11 [KO:K05417]
123787227  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
123787247  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
123787248  IL23A; interleukin-23 subunit alpha [KO:K05426]
123787291  IL22; interleukin-22 [KO:K05445]
123787293  IL26; interleukin-26 [KO:K05446]
123787294  IFNG; interferon gamma [KO:K04687]
123787360  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X1 [KO:K16063] [EC:2.3.2.-]
123787450  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
123787468  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
123787668  IL13RA1; LOW QUALITY PROTEIN: interleukin-13 receptor subunit alpha-1 [KO:K05076]
123787744  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
123788156  LIF; leukemia inhibitory factor [KO:K05419]
123788158  OSM; oncostatin-M isoform X1 [KO:K05418]
123788299  [KO:K05073]
123788411  IL20RB; interleukin-20 receptor subunit beta [KO:K05137]
123788422  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123788629  IL12B; interleukin-12 subunit beta [KO:K05425]
123788681  IL6; interleukin-6 [KO:K05405]
123789555  [KO:K05424]
123790182  IL6ST; interleukin-6 receptor subunit beta [KO:K05060]
123790366  IL4; interleukin-4 [KO:K05430]
123790368  IL5; interleukin-5 [KO:K05428]
123790515  IL31RA; LOW QUALITY PROTEIN: interleukin-31 receptor subunit alpha [KO:K22630]
123790532  IL9; interleukin-9 [KO:K05432]
123790538  IL13; interleukin-13 [KO:K05435]
123790540  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
123790541  [KO:K04736]
123791081  PRL; prolactin [KO:K05439]
123791373  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123792610  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
123792708  [KO:K07293] [EC:3.1.3.48]
123793113  IL21; interleukin-21 [KO:K05434]
123793114  IL2; interleukin-2 [KO:K05429]
123793257  IL15; interleukin-15 isoform X1 [KO:K05433]
123793291  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123793362  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
123793473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123793748  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
123793801  MPL; thrombopoietin receptor [KO:K05082]
123794983  IL23R; interleukin-23 receptor [KO:K05065]
123795331  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
123795343  LEPR; leptin receptor isoform X1 [KO:K05062]
123795350  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
123795756  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
123796821  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
123797095  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
123797206  IL13RA2; interleukin-13 receptor subunit alpha-2 [KO:K05077]
123797942  IL7; interleukin-7 [KO:K05431]
123798145  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
123798149  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
123798185  AOX1; aldehyde oxidase isoform X1 [KO:K00157] [EC:1.2.3.1]
123798186  [KO:K00157] [EC:1.2.3.1]
123798188  [KO:K00157] [EC:1.2.3.1]
123798668  IFNL3; interferon lambda-3 [KO:K22669]
123798690  BCL2L1; bcl-2-like protein 1 [KO:K04570]
123798704  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
123798731  [KO:K05447]
123799153  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
123799809  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123800228  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123800746  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
123800841  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
123801580  IL12A; interleukin-12 subunit alpha [KO:K05406]
123801741  IL27RA; interleukin-27 receptor subunit alpha [KO:K19598]
123801908  MYC; myc proto-oncogene protein [KO:K04377]
123802053  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123802289  IL15RA; LOW QUALITY PROTEIN: interleukin-15 receptor subunit alpha [KO:K05074]
123802327  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
123802515  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
123802758  CSF2RA; granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
123802767  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
123802771  CRLF2; cytokine receptor-like factor 2 [KO:K05078]
123802882  SOCS7; LOW QUALITY PROTEIN: suppressor of cytokine signaling 7 [KO:K04699]
123802938  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123803168  GH1; somatotropin [KO:K05438]
123803186  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
123803198  [KO:K05640]
123803346  IFNGR1; interferon gamma receptor 1 [KO:K05132]
123803350  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
123803369  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
123803539  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
123803639  PDGFRB; LOW QUALITY PROTEIN: platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
123804080  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
Reference
  Authors
Harrison DA
  Title
The Jak/STAT pathway.
  Journal
Cold Spring Harb Perspect Biol 4:a011205 (2012)
DOI:10.1101/cshperspect.a011205
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
uar04010  MAPK signaling pathway
uar04060  Cytokine-cytokine receptor interaction
uar04110  Cell cycle
uar04120  Ubiquitin mediated proteolysis
uar04151  PI3K-Akt signaling pathway
uar04210  Apoptosis
KO pathway
ko04630   

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