KEGG   PATHWAY: cfa04630
Entry
cfa04630                    Pathway                                
Name
JAK-STAT signaling pathway - Canis lupus familiaris (dog)
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
cfa04630  JAK-STAT signaling pathway
cfa04630

Other DBs
GO: 0007259
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
403989  IL2; interleukin-2 precursor [KO:K05429]
403785  IL4; interleukin-4 precursor [KO:K05430]
751768  IL7; interleukin-7 precursor [KO:K05431]
100682918  IL9; interleukin-9 [KO:K05432]
403584  IL15; interleukin-15 [KO:K05433]
442935  IL21; interleukin-21 precursor [KO:K05434]
607671  TSLP; thymic stromal lymphopoietin isoform X5 [KO:K05436]
403870  IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068]
403439  IL2RB; interleukin-2 receptor subunit beta isoform 2 precursor [KO:K05069]
403851  IL2RG; cytokine receptor common subunit gamma precursor [KO:K05070]
489957  IL4R; interleukin-4 receptor subunit alpha isoform X2 [KO:K05071]
612582  IL7R; interleukin-7 receptor subunit alpha isoform X2 [KO:K05072]
100684807  LOW QUALITY PROTEIN: interleukin-9 receptor [KO:K05073]
487141  IL15RA; interleukin-15 receptor subunit alpha isoform X1 [KO:K05074]
608011  IL21R; interleukin-21 receptor [KO:K05075]
491709  CRLF2; cytokine receptor-like factor 2 isoform X1 [KO:K05078]
481497  IL3; interleukin-3 precursor [KO:K04736]
403790  IL5; interleukin-5 precursor [KO:K05428]
403923  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
609293  IL3RA; interleukin-3 receptor subunit alpha isoform X16 [KO:K04737]
476553  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
609266  CSF2RA; granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
100686341  granulocyte-macrophage colony-stimulating factor receptor subunit alpha-like isoform X2 [KO:K05066]
481276  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
403985  IL6; interleukin-6 precursor [KO:K05405]
442990  IL13; interleukin-13 precursor [KO:K05435]
607880  IL27; interleukin-27 subunit alpha isoform X1 [KO:K22629]
100302725  IL31; interleukin-31 precursor [KO:K22631]
611921  OSM; oncostatin-M [KO:K05418]
403449  LIF; leukemia inhibitory factor precursor [KO:K05419]
483464  CNTF; ciliary neurotrophic factor [KO:K05420]
403821  CTF1; cardiotrophin-1 [KO:K05422]
489915  cardiotrophin-2-like [KO:K24382]
483697  CLCF1; cardiotrophin-like cytokine factor 1 isoform X2 [KO:K05421]
612271  IL6R; interleukin-6 receptor subunit alpha isoform X3 [KO:K05055]
403545  IL6ST; interleukin-6 receptor subunit beta precursor [KO:K05060]
481588  IL11RA; interleukin-11 receptor subunit alpha isoform X1 [KO:K05056]
403623  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X1 [KO:K05076]
403622  IL13RA2; interleukin-13 receptor subunit alpha-2 precursor [KO:K05077]
484907  IL27RA; interleukin-27 receptor subunit alpha [KO:K19598]
487212  IL31RA; interleukin-31 receptor subunit alpha isoform X2 [KO:K22630]
489223  OSMR; oncostatin-M-specific receptor subunit beta isoform X1 [KO:K05057]
449478  LIFR; leukemia inhibitory factor receptor precursor [KO:K05058]
442941  CNTFR; ciliary neurotrophic factor receptor subunit alpha precursor [KO:K05059]
403628  IL10; interleukin-10 precursor [KO:K05443]
490265  IL19; interleukin-19 [KO:K05444]
481153  IL22; interleukin-22 [KO:K05445]
609203  IL20; interleukin-20 isoform X1 [KO:K22667]
609213  IL24; interleukin-24 isoform X1 [KO:K22668]
608923  IL26; interleukin-26 [KO:K05446]
610823  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
478404  IL10RB; interleukin-10 receptor subunit beta isoform X2 [KO:K05135]
484002  IL20RA; interleukin-20 receptor subunit alpha isoform X2 [KO:K05136]
610961  IL20RB; interleukin-20 receptor subunit beta isoform X3 [KO:K05137]
612279  IL22RA1; interleukin-22 receptor subunit alpha-1 isoform X2 [KO:K05138]
100856046  IL22RA2; interleukin-22 receptor subunit alpha-2 isoform X2 [KO:K05139]
403977  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
403976  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
481110  IL23A; interleukin-23 subunit alpha [KO:K05426]
484828  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
489550  IL12RB2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
609732  IL23R; interleukin-23 receptor [KO:K05065]
404002  EPO; LOW QUALITY PROTEIN: erythropoietin [KO:K05437]
403795  GH1; somatotropin precursor [KO:K05438]
488241  PRL; prolactin precursor [KO:K05439]
100855822  THPO; thrombopoietin isoform X1 [KO:K06854]
608246  CSF3; granulocyte colony-stimulating factor [KO:K05423]
403616  LEP; leptin precursor [KO:K05424]
484943  EPOR; erythropoietin receptor precursor [KO:K05079]
403721  GHR; growth hormone receptor precursor [KO:K05080]
479363  PRLR; prolactin receptor isoform X2 [KO:K05081]
610801  MPL; thrombopoietin receptor isoform X1 [KO:K05082]
607605  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
450207  LEPR; leptin receptor [KO:K05062]
474181  IFNA7; interferon alpha-1/2 precursor [KO:K05414]
442934  IFNA5; interferon alpha-3 precursor [KO:K05414]
611406  interferon alpha-1/2-like isoform X1 [KO:K05414]
100686162  interferon alpha-2-like [KO:K05414]
100682977  interferon alpha-1/2 isoform X5 [KO:K05414]
100683045  LOW QUALITY PROTEIN: interferon alpha-1/2 isoform X5 [KO:K05414]
100683567  interferon alpha-1/2-like isoform X1 [KO:K05414]
100688005  interferon alpha-1/2 [KO:K05414]
100685213  interferon alpha-1/2 [KO:K05414]
100688084  interferon alpha-1/2 isoform X1 [KO:K05414]
481558  IFNB1; interferon beta precursor [KO:K05415]
111089992  IFNE; interferon epsilon isoform X1 [KO:K05442]
100855436  IFNK; interferon kappa [KO:K05441]
611377  IL29L; interleukin 29-like precursor [KO:K05447]
612539  IFNL1; interferon lambda-1 [KO:K05447]
119870346  IFNL3; interferon lambda-3 [KO:K22669]
609830  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
100856468  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
612276  IFNLR1; interferon lambda receptor 1 [KO:K05140]
403801  IFNG; interferon gamma precursor [KO:K04687]
100856077  IFNGR1; interferon gamma receptor 1 [KO:K05132]
487739  IFNGR2; interferon gamma receptor 2 isoform X3 [KO:K05133]
403657  EGF; pro-epidermal growth factor precursor [KO:K04357]
491597  PDGFA; platelet-derived growth factor subunit A precursor [KO:K04359]
442986  PDGFB; platelet-derived growth factor subunit B precursor [KO:K17386]
404306  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
442860  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
442985  PDGFRB; platelet-derived growth factor receptor beta precursor [KO:K05089] [EC:2.7.10.1]
442952  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
484185  JAK2; tyrosine-protein kinase JAK2 isoform X13 [KO:K04447] [EC:2.7.10.2]
610004  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
476714  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
488449  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
481111  STAT2; signal transducer and activator of transcription 2 isoform X2 [KO:K11221]
490967  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
478845  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
490968  STAT5A; signal transducer and activator of transcription 5A isoform X2 [KO:K11223]
490969  STAT5B; signal transducer and activator of transcription 5B isoform X2 [KO:K11224]
100142679  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
607899  IRF9; interferon regulatory factor 9 [KO:K04693]
484757  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
490006  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
100855737  SOCS2; suppressor of cytokine signaling 2 isoform X3 [KO:K04695]
442949  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100687271  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
474581  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
491039  SOCS7; suppressor of cytokine signaling 7 [KO:K04699]
100856303  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
100684658  LOW QUALITY PROTEIN: suppressor of cytokine signaling 6-like [KO:K04699]
403416  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
403537  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
403618  BCL2L1; bcl-2-like protein 1 [KO:K04570]
481772  PIM1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
403924  MYC; myc proto-oncogene protein [KO:K04377]
449028  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
611782  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
608847  CCND3; G1/S-specific cyclin-D3 isoform X3 [KO:K10152]
474890  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
608849  AOX2; aldehyde oxidase 2 [KO:K00157] [EC:1.2.3.1]
488467  AOX4; aldehyde oxidase 4 [KO:K00157] [EC:1.2.3.1]
480495  GFAP; glial fibrillary acidic protein isoform X2 [KO:K05640]
476150  STAM2; signal transducing adapter molecule 2 isoform X2 [KO:K04705]
477990  STAM; signal transducing adapter molecule 1 isoform X1 [KO:K04705]
490563  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
486717  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
479866  CREBBP; CREB-binding protein isoform X8 [KO:K04498] [EC:2.3.1.48]
100684945  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
478350  PIAS1; E3 SUMO-protein ligase PIAS1 isoform X2 [KO:K04706] [EC:2.3.2.-]
480147  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X3 [KO:K16063] [EC:2.3.2.-]
483160  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X2 [KO:K16064] [EC:2.3.2.-]
485049  PIAS4; E3 SUMO-protein ligase PIAS4 isoform X3 [KO:K16065] [EC:2.3.2.27]
492162  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
477488  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100683481  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
483312  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
490682  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
403735  HRAS; GTPase HRas isoform 1 [KO:K02833]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
488084  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
489644  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
477085  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
609956  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
487235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100856339  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
442964  AKT3; RAC-gamma serine/threonine-protein kinase isoform X8 [KO:K04456] [EC:2.7.11.1]
449021  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
490878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
478232  MTOR; serine/threonine-protein kinase mTOR isoform X5 [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
cfa04010  MAPK signaling pathway
cfa04060  Cytokine-cytokine receptor interaction
cfa04110  Cell cycle
cfa04120  Ubiquitin mediated proteolysis
cfa04151  PI3K-Akt signaling pathway
cfa04210  Apoptosis
KO pathway
ko04630   
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