KEGG   PATHWAY: pcw04630
Entry
pcw04630                    Pathway                                
Name
JAK-STAT signaling pathway - Phascolarctos cinereus (koala)
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
pcw04630  JAK-STAT signaling pathway
pcw04630

Other DBs
GO: 0007259
Organism
Phascolarctos cinereus (koala) [GN:pcw]
Gene
110223001  interleukin-2-like [KO:K05429]
110211817  IL4; interleukin-4 [KO:K05430]
110199192  IL7; interleukin-7 isoform X1 [KO:K05431]
110211673  IL9; LOW QUALITY PROTEIN: interleukin-9 [KO:K05432]
110210781  IL15; interleukin-15 isoform X1 [KO:K05433]
110222957  IL21; interleukin-21 [KO:K05434]
110198993  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
110205742  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
110201024  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
110221658  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
110214720  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
110221831  LOW QUALITY PROTEIN: interleukin-9 receptor-like [KO:K05073]
110198995  IL15RA; interleukin-15 receptor subunit alpha [KO:K05074]
110221598  IL21R; interleukin-21 receptor [KO:K05075]
110212747  CRLF2; cytokine receptor-like factor 2 isoform X1 [KO:K05078]
110211821  IL5; interleukin-5 [KO:K05428]
110211657  granulocyte-macrophage colony-stimulating factor-like [KO:K05427]
110212842  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
110195632  IL5RA; interleukin-5 receptor subunit alpha isoform X1 [KO:K05067]
110212746  CSF2RA; granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
110205736  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
110213115  IL6; interleukin-6 [KO:K05405]
110220139  IL11; interleukin-11 isoform X1 [KO:K05417]
110211655  IL13; interleukin-13 [KO:K05435]
110222073  IL27; LOW QUALITY PROTEIN: interleukin-27 subunit alpha [KO:K22629]
110215344  OSM; oncostatin-M isoform X1 [KO:K05418]
110215332  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
110200718  CNTF; ciliary neurotrophic factor [KO:K05420]
110223186  CTF1; cardiotrophin-1 isoform X1 [KO:K05422]
110223157  cardiotrophin-2-like [KO:K24382]
110195515  CLCF1; cardiotrophin-like cytokine factor 1 isoform X1 [KO:K05421]
110211977  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
110215675  IL6ST; interleukin-6 receptor subunit beta [KO:K05060]
110194547  IL11RA; interleukin-11 receptor subunit alpha isoform X1 [KO:K05056]
110192322  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X1 [KO:K05076]
110192377  IL13RA2; interleukin-13 receptor subunit alpha-2 isoform X1 [KO:K05077]
110214240  IL27RA; interleukin-27 receptor subunit alpha isoform X1 [KO:K19598]
110215657  IL31RA; interleukin-31 receptor subunit alpha isoform X1 [KO:K22630]
110214934  OSMR; LOW QUALITY PROTEIN: oncostatin-M-specific receptor subunit beta [KO:K05057]
110214917  LIFR; leukemia inhibitory factor receptor [KO:K05058]
110194545  CNTFR; ciliary neurotrophic factor receptor subunit alpha [KO:K05059]
110219537  IL10; interleukin-10 [KO:K05443]
110219595  interleukin-19-like isoform X1 [KO:K05444]
110211145  IL22; interleukin-22 [KO:K05445]
110219594  IL24; interleukin-24 [KO:K22668]
110211144  IL26; interleukin-26 [KO:K05446]
110207176  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
110214852  interleukin-10 receptor subunit beta-like [KO:K05135]
110208926  IL20RA; interleukin-20 receptor subunit alpha isoform X1 [KO:K05136]
110208253  IL20RB; interleukin-20 receptor subunit beta isoform X1 [KO:K05137]
110206073  IL22RA1; interleukin-22 receptor subunit alpha-1 isoform X1 [KO:K05138]
110208927  IL22RA2; interleukin-22 receptor subunit alpha-2 isoform X1 [KO:K05139]
110210080  IL12A; interleukin-12 subunit alpha [KO:K05406]
110212378  IL12B; interleukin-12 subunit beta [KO:K05425]
110210932  IL23A; interleukin-23 subunit alpha isoform X1 [KO:K05426]
110223476  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
110212954  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
110212868  IL23R; interleukin-23 receptor isoform X1 [KO:K05065]
110202831  EPO; erythropoietin [KO:K05437]
110215837  somatotropin [KO:K05438]
110208793  PRL; prolactin [KO:K05439]
110221303  THPO; thrombopoietin isoform X1 [KO:K06854]
110215806  CSF3; granulocyte colony-stimulating factor [KO:K05423]
110219143  LEP; leptin [KO:K05424]
110214315  EPOR; erythropoietin receptor isoform X1 [KO:K05079]
110216101  GHR; growth hormone receptor [KO:K05080]
110214629  PRLR; LOW QUALITY PROTEIN: prolactin receptor [KO:K05081]
110206350  CSF3R; LOW QUALITY PROTEIN: granulocyte colony-stimulating factor receptor [KO:K05061]
110212977  LEPR; leptin receptor [KO:K05062]
110201183  interferon tau-2-like [KO:K05414]
110199230  interferon tau-2-like [KO:K05414]
110199240  interferon omega-1-like [KO:K05414]
110199247  interferon omega-1-like [KO:K05414]
110199249  interferon tau-2-like [KO:K05414]
110199250  interferon tau-2-like [KO:K05414]
110199251  interferon tau-2-like [KO:K05414]
110199253  interferon tau-2-like [KO:K05414]
110199254  interferon tau-2-like [KO:K05414]
110199255  interferon tau-2-like [KO:K05414]
110201199  interferon tau-2-like [KO:K05414]
110201202  interferon tau-2-like [KO:K05414]
110201203  interferon alpha-2-like [KO:K05414]
110199211  interferon beta-like [KO:K05415]
110199212  interferon beta-like [KO:K05415]
110199213  interferon beta-like [KO:K05415]
110199216  interferon beta-like [KO:K05415]
110199218  interferon beta-like [KO:K05415]
110198621  IFNK; interferon kappa [KO:K05441]
110198176  interferon lambda-3-like isoform X1 [KO:K22669]
110214849  interferon alpha/beta receptor 1-like [KO:K05130]
110214853  IFNAR2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131]
110206074  IFNLR1; interferon lambda receptor 1 isoform X1 [KO:K05140]
110211092  IFNG; interferon gamma isoform X1 [KO:K04687]
110208928  IFNGR1; interferon gamma receptor 1 [KO:K05132]
110214784  IFNGR2; interferon gamma receptor 2 [KO:K05133]
110218605  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
110201572  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
110205795  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
110204990  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
110200158  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
110192821  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
110212891  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
110221618  JAK2; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
110223345  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
110214168  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
110213248  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
110210934  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
110198372  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
110213328  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
110198414  LOW QUALITY PROTEIN: signal transducer and activator of transcription 5A-like [KO:K11223]
110198412  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
110210962  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
110195167  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
110216971  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
110198338  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
110205866  suppressor of cytokine signaling 1-like [KO:K04694]
110221772  SOCS2; suppressor of cytokine signaling 2 isoform X1 [KO:K04695]
110193931  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
110211768  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
110218504  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
110215753  SOCS7; suppressor of cytokine signaling 7 isoform X1 [KO:K04699]
110207825  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
110214751  BCL2; LOW QUALITY PROTEIN: apoptosis regulator Bcl-2 [KO:K02161]
110220506  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 isoform X1 [KO:K02539]
110211412  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
110217282  PIM1; LOW QUALITY PROTEIN: serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
110216083  MYC; myc proto-oncogene protein [KO:K04377]
110197171  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
110218698  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
110203289  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
110217257  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
110207269  aldehyde oxidase 3-like isoform X1 [KO:K00157] [EC:1.2.3.1]
110207271  AOX1; aldehyde oxidase [KO:K00157] [EC:1.2.3.1]
110197327  aldehyde oxidase 2-like isoform X1 [KO:K00157] [EC:1.2.3.1]
110215851  GFAP; glial fibrillary acidic protein [KO:K05640]
110194504  STAM; signal transducing adapter molecule 1 [KO:K04705]
110196886  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
110207799  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
110213796  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
110205826  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110214481  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
110205743  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
110207973  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X1 [KO:K16063] [EC:2.3.2.-]
110219948  PIAS3; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS3 [KO:K16064] [EC:2.3.2.-]
110197458  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
110196502  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
110203391  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
110201173  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
110219266  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
110211774  SOS2; son of sevenless homolog 2 [KO:K03099]
110201388  SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
110202954  HRAS; GTPase HRas isoform X1 [KO:K02833]
110204892  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110204454  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110208219  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110199476  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
110223395  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110216530  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110209293  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
110205475  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110202713  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110203042  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110199207  MTOR; LOW QUALITY PROTEIN: 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
pcw04010  MAPK signaling pathway
pcw04060  Cytokine-cytokine receptor interaction
pcw04110  Cell cycle
pcw04120  Ubiquitin mediated proteolysis
pcw04151  PI3K-Akt signaling pathway
pcw04210  Apoptosis
KO pathway
ko04630   
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