KEGG   PATHWAY: oas04630
Entry
oas04630                    Pathway                                
Name
JAK-STAT signaling pathway - Ovis aries (sheep)
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
oas04630  JAK-STAT signaling pathway
oas04630

Other DBs
GO: 0007259
Organism
Ovis aries (sheep) [GN:oas]
Gene
443401  IL2; interleukin-2 precursor [KO:K05429]
101122781  IL4; interleukin-4 precursor [KO:K05430]
443341  IL7; interleukin-7 precursor [KO:K05431]
101105494  IL9; interleukin-9 [KO:K05432]
443056  IL15; interleukin-15 precursor [KO:K05433]
100862657  IL21; interleukin-21 precursor [KO:K05434]
443435  IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068]
101107088  IL2RB; interleukin-2 receptor subunit beta isoform X2 [KO:K05069]
101103538  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
101109063  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
101111126  IL7R; interleukin-7 receptor subunit alpha isoform X3 [KO:K05072]
114110650  IL9R; interleukin-9 receptor isoform X2 [KO:K05073]
101107377  IL15RA; interleukin-15 receptor subunit alpha isoform X1 [KO:K05074]
100820753  IL21R; interleukin-21 receptor precursor [KO:K05075]
101113732  CRLF2; cytokine receptor-like factor 2 isoform X1 [KO:K05078]
443438  IL3; interleukin-3 precursor [KO:K04736]
443350  IL5; interleukin-5 precursor [KO:K05428]
443400  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
101113991  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
101111837  IL5RA; interleukin-5 receptor subunit alpha isoform X1 [KO:K05067]
101115509  granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X7 [KO:K05066]
101123199  CSF2RB; cytokine receptor common subunit beta isoform X1 [KO:K04738]
443406  IL6; interleukin-6 precursor [KO:K05405]
114118064  IL11; interleukin-11 [KO:K05417]
664707  IL13; interleukin-13 precursor [KO:K05435]
101122495  IL27; interleukin-27 subunit alpha [KO:K22629]
101122466  OSM; oncostatin-M [KO:K05418]
101110180  LIF; leukemia inhibitory factor [KO:K05419]
101107894  CNTF; ciliary neurotrophic factor [KO:K05420]
101104201  CTF1; cardiotrophin-1 isoform X3 [KO:K05422]
114110595  cardiotrophin-2-like [KO:K24382]
121817918  cardiotrophin-2-like [KO:K24382]
101108788  CLCF1; cardiotrophin-like cytokine factor 1 isoform X2 [KO:K05421]
101103369  IL6R; interleukin-6 receptor subunit alpha isoform X1 [KO:K05055]
101113174  IL6ST; interleukin-6 receptor subunit beta [KO:K05060]
101120724  IL11RA; interleukin-11 receptor subunit alpha [KO:K05056]
443518  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X2 [KO:K05076]
101108025  IL13RA2; interleukin-13 receptor subunit alpha-2 isoform X2 [KO:K05077]
101102232  IL27RA; interleukin-27 receptor subunit alpha isoform X1 [KO:K19598]
101113274  IL31RA; interleukin-31 receptor subunit alpha [KO:K22630]
101105948  OSMR; oncostatin-M-specific receptor subunit beta isoform X1 [KO:K05057]
101106364  LIFR; leukemia inhibitory factor receptor isoform X3 [KO:K05058]
100885760  CNTFR; ciliary neurotrophic factor receptor subunit alpha isoform X1 [KO:K05059]
443342  IL10; interleukin-10 precursor [KO:K05443]
101112663  IL19; interleukin-19 [KO:K05444]
100885770  IL22; interleukin-22 precursor [KO:K05445]
101112916  IL20; interleukin-20 [KO:K22667]
101113424  IL24; interleukin-24 [KO:K22668]
101107268  IL26; interleukin-26 [KO:K05446]
101120946  IL10RA; interleukin-10 receptor subunit alpha isoform X1 [KO:K05134]
105609264  IL10RB; interleukin-10 receptor subunit beta [KO:K05135]
101112653  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
101113034  IL20RB; interleukin-20 receptor subunit beta isoform X2 [KO:K05137]
101118168  IL22RA1; interleukin-22 receptor subunit alpha-1 isoform X1 [KO:K05138]
101121781  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
443064  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
443472  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
100462692  IL23A; interleukin-23 subunit alpha precursor [KO:K05426]
101110054  IL12RB1; interleukin-12 receptor subunit beta-1 precursor [KO:K05063]
100820736  IL12RB2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
101103528  IL23R; interleukin-23 receptor [KO:K05065]
443302  EPO; erythropoietin precursor [KO:K05437]
443329  GH; somatotropin precursor [KO:K05438]
114116958  somatotropin isoform X2 [KO:K05438]
100126189  PRP1; prolactin-related protein 1 precursor [KO:K05439]
443319  chorionic somatomammotropin hormone precursor [KO:K05439]
100127213  PRP2; prolactin-related protein-2 precursor [KO:K05439]
101102463  placental prolactin-related protein 3-like [KO:K05439]
443317  PRL; prolactin precursor [KO:K05439]
101109399  placental prolactin-related protein 3-like [KO:K05439]
101109654  placental prolactin-related protein 3-like isoform X1 [KO:K05439]
101110459  chorionic somatomammotropin hormone 1-like [KO:K05439]
101102796  chorionic somatomammotropin hormone 2-like isoform X2 [KO:K05439]
105613815  placental prolactin-related protein 3-like isoform X1 [KO:K05439]
114108610  placental prolactin-related protein 1-like isoform X1 [KO:K05439]
101109921  placental prolactin-related protein 1-like [KO:K05439]
114109603  placental prolactin-related protein 3-like [KO:K05439]
114109612  placental prolactin-related protein 4-like [KO:K05439]
101119601  THPO; thrombopoietin isoform X1 [KO:K06854]
443523  CSF3; granulocyte colony-stimulating factor isoform X1 [KO:K05423]
443534  LEP; leptin [KO:K05424]
443227  EPOR; erythropoietin receptor isoform X2 [KO:K05079]
443333  GHR; growth hormone receptor precursor [KO:K05080]
101110279  MPL; thrombopoietin receptor [KO:K05082]
101118070  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
443264  LEPR; leptin receptor [KO:K05062]
101111435  interferon alpha-H-like [KO:K05414]
105601948  interferon alpha-H-like [KO:K05414]
492823  IFN1; interferon alpha-1 [KO:K05414]
101102963  interferon alpha-H-like [KO:K05414]
101105135  interferon alpha-H [KO:K05414]
101103872  interferon alpha-2-like [KO:K05414]
114113084  interferon alpha-14-like [KO:K05414]
114113089  interferon alpha-2-like [KO:K05414]
114113090  interferon alpha-H-like [KO:K05414]
114112827  interferon alpha-3-like [KO:K05414]
101105632  interferon alpha-H-like [KO:K05414]
121818512  interferon alpha-2-like [KO:K05414]
101103702  interferon beta-2-like [KO:K05415]
101103376  interferon beta-2-like [KO:K05415]
101103623  interferon beta-2 [KO:K05415]
114113004  interferon beta-2-like [KO:K05415]
114113016  interferon beta-2-like [KO:K05415]
114113206  interferon beta-2-like [KO:K05415]
114112819  interferon beta-2-like [KO:K05415]
114112835  interferon beta-2-like [KO:K05415]
114112840  interferon beta-2-like [KO:K05415]
114112883  interferon beta-2 [KO:K05415]
114112830  interferon beta-2-like [KO:K05415]
121818657  interferon beta-2-like [KO:K05415]
101104211  IFNE; interferon epsilon [KO:K05442]
101111520  IFNK; interferon kappa [KO:K05441]
101115898  interferon lambda-3 [KO:K22669]
101116168  interferon lambda-3-like [KO:K22669]
105608320  interferon omega-1-like [KO:K05440]
101106658  LOW QUALITY PROTEIN: interferon tau [KO:K05440]
114113003  interferon omega-1-like [KO:K05440]
114113005  interferon omega-1-like [KO:K05440]
114113006  interferon omega-1 [KO:K05440]
114113008  interferon omega-1-like [KO:K05440]
114113019  interferon omega-1-like [KO:K05440]
114113207  interferon omega-1-like [KO:K05440]
114113208  interferon omega-1-like [KO:K05440]
114112818  interferon omega-1-like [KO:K05440]
114112820  interferon omega-1-like [KO:K05440]
114112821  interferon omega-1-like [KO:K05440]
114112822  interferon omega-1-like [KO:K05440]
114112825  interferon omega-1-like [KO:K05440]
114112826  interferon omega-1-like [KO:K05440]
114112828  interferon omega-1-like [KO:K05440]
114112829  interferon omega-1-like [KO:K05440]
114112832  interferon omega-1 [KO:K05440]
114112837  interferon omega-1-like [KO:K05440]
114112842  interferon omega-1-like [KO:K05440]
114112843  interferon omega-1-like [KO:K05440]
106990900  interferon omega-1-like [KO:K05440]
101106400  interferon omega-1-like [KO:K05440]
114112824  interferon omega-1-like [KO:K05440]
114113147  interferon omega-1-like [KO:K05440]
121818508  interferon omega-1-like [KO:K05440]
121818509  interferon omega-1-like [KO:K05440]
443126  IFNAR1; interferon alpha/beta receptor 1 precursor [KO:K05130]
443363  IFNAR2; interferon alpha/beta receptor 2 precursor [KO:K05131]
101119890  IFNLR1; interferon lambda receptor 1 [KO:K05140]
443396  IFNG; interferon gamma precursor [KO:K04687]
101112907  IFNGR1; interferon gamma receptor 1 isoform X2 [KO:K05132]
101122484  IFNGR2; interferon gamma receptor 2 isoform X2 [KO:K05133]
114110564  PDGFA; platelet-derived growth factor subunit A isoform X2 [KO:K04359]
443545  PDGFB; platelet-derived growth factor subunit B precursor [KO:K17386]
780479  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101106012  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
101122783  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
101110716  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101113909  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101112816  JAK3; tyrosine-protein kinase JAK3 isoform X2 [KO:K11218] [EC:2.7.10.2]
101117248  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100307049  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101108211  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
100294659  STAT3; signal transducer and activator of transcription 3 isoform X10 [KO:K04692]
101117562  STAT4; signal transducer and activator of transcription 4 isoform X2 [KO:K11222]
443419  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
101122961  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
101102134  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
101116656  IRF9; interferon regulatory factor 9 isoform X3 [KO:K04693]
101119259  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
101107324  SOCS1; suppressor of cytokine signaling 1 isoform X2 [KO:K04694]
101115017  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
100294595  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101117935  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
101109082  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
101123392  SOCS7; suppressor of cytokine signaling 7 isoform X1 [KO:K04699]
101112276  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
101119602  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
554329  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
105610887  LOW QUALITY PROTEIN: bcl-2-like protein 1 [KO:K04570]
443061  BCL2L1; bcl-2-like protein 1 [KO:K04570]
101106158  bcl-2-like protein 1 [KO:K04570]
100272002  PIM1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
443447  MYC; myc proto-oncogene protein [KO:K04377]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100147799  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100147798  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
100302083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101104557  aldehyde oxidase 1 [KO:K00157] [EC:1.2.3.1]
101104808  aldehyde oxidase 4-like [KO:K00157] [EC:1.2.3.1]
101102548  aldehyde oxidase 2 isoform X1 [KO:K00157] [EC:1.2.3.1]
443220  GFAP; glial fibrillary acidic protein isoform X1 [KO:K05640]
101111214  STAM; signal transducing adapter molecule 1 isoform X1 [KO:K04705]
101117649  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
101106987  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
101108643  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
101110136  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101123600  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101104493  PIAS1; E3 SUMO-protein ligase PIAS1 isoform X2 [KO:K04706] [EC:2.3.2.-]
101112782  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X2 [KO:K16063] [EC:2.3.2.-]
101116875  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X2 [KO:K16064] [EC:2.3.2.-]
101116396  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
100307044  FHL1; four and a half LIM domains protein 1 [KO:K14365]
101114308  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X3 [KO:K07293] [EC:3.1.3.48]
101107037  tyrosine-protein phosphatase non-receptor type 11-like isoform X4 [KO:K07293] [EC:3.1.3.48]
101109893  GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364]
114110058  growth factor receptor-bound protein 2 [KO:K04364]
101118865  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
101102732  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
114114919  GTPase HRas-like [KO:K02833]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100271659  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
oas04010  MAPK signaling pathway
oas04060  Cytokine-cytokine receptor interaction
oas04110  Cell cycle
oas04120  Ubiquitin mediated proteolysis
oas04151  PI3K-Akt signaling pathway
oas04210  Apoptosis
KO pathway
ko04630   
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