KEGG   PATHWAY: ocu04630
Entry
ocu04630                    Pathway                                
Name
JAK-STAT signaling pathway - Oryctolagus cuniculus (rabbit)
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
ocu04630  JAK-STAT signaling pathway
ocu04630

Other DBs
GO: 0007259
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100302458  IL2; interleukin-2 isoform 1 precursor [KO:K05429]
100302454  IL4; interleukin-4 isoform 1 precursor [KO:K05430]
100345409  interleukin-7 isoform X1 [KO:K05431]
100340820  interleukin-9 [KO:K05432]
100009017  IL15; interleukin-15 precursor [KO:K05433]
100344172  interleukin-21 [KO:K05434]
103349580  thymic stromal lymphopoietin [KO:K05436]
100338113  interleukin-2 receptor subunit alpha [KO:K05068]
100358489  interleukin-2 receptor subunit alpha [KO:K05068]
103346218  interleukin-2 receptor subunit beta [KO:K05069]
103351862  cytokine receptor common subunit gamma [KO:K05070]
100337721  interleukin-4 receptor subunit alpha [KO:K05071]
100343726  interleukin-7 receptor subunit alpha [KO:K05072]
100356855  LOW QUALITY PROTEIN: interleukin-9 receptor [KO:K05073]
100358749  interleukin-15 receptor subunit alpha [KO:K05074]
100359262  interleukin-15 receptor subunit alpha [KO:K05074]
127487864  interleukin-15 receptor subunit alpha-like isoform X1 [KO:K05074]
103348594  interleukin-21 receptor [KO:K05075]
103352517  cytokine receptor-like factor 2 [KO:K05078]
100358075  interleukin-5 [KO:K05428]
100328720  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
103345135  interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
100347606  interleukin-5 receptor subunit alpha [KO:K05067]
100346676  granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
100349996  cytokine receptor common subunit beta [KO:K04738]
100008733  IL6; interleukin-6 precursor [KO:K05405]
127486876  interleukin-11 [KO:K05417]
100358676  interleukin-13 isoform X3 [KO:K05435]
100349321  interleukin-27 subunit alpha [KO:K22629]
100342491  oncostatin-M [KO:K05418]
100358914  LIF; leukemia inhibitory factor precursor [KO:K05419]
100009117  CNTF; ciliary neurotrophic factor [KO:K05420]
100354643  LOW QUALITY PROTEIN: cardiotrophin-1 [KO:K05422]
108175610  cardiotrophin-2 [KO:K24382]
100356265  cardiotrophin-like cytokine factor 1 isoform X1 [KO:K05421]
100347752  interleukin-6 receptor subunit alpha isoform X1 [KO:K05055]
100349330  interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
103351784  interleukin-11 receptor subunit alpha isoform X1 [KO:K05056]
100351788  interleukin-13 receptor subunit alpha-1 [KO:K05076]
100348025  interleukin-13 receptor subunit alpha-2 isoform X1 [KO:K05077]
103347059  interleukin-27 receptor subunit alpha isoform X1 [KO:K19598]
100347492  interleukin-31 receptor subunit alpha isoform X2 [KO:K22630]
100356631  oncostatin-M-specific receptor subunit beta isoform X2 [KO:K05057]
100303762  leukemia inhibitory factor receptor isoform X1 [KO:K05058]
100349367  ciliary neurotrophic factor receptor subunit alpha [KO:K05059]
100008701  IL10; interleukin-10 precursor [KO:K05443]
100353950  interleukin-19 [KO:K05444]
100348980  interleukin-22 [KO:K05445]
100353705  interleukin-20 isoform X1 [KO:K22667]
100348730  interleukin-26 [KO:K05446]
100354902  interleukin-10 receptor subunit alpha [KO:K05134]
100338351  interleukin-10 receptor subunit beta [KO:K05135]
100341271  interleukin-20 receptor subunit alpha isoform X1 [KO:K05136]
100349338  interleukin-20 receptor subunit beta isoform X1 [KO:K05137]
100344077  interleukin-22 receptor subunit alpha-1 [KO:K05138]
100341531  interleukin-22 receptor subunit alpha-2 isoform X1 [KO:K05139]
100349007  interleukin-12 subunit alpha [KO:K05406]
100354852  interleukin-12 subunit beta [KO:K05425]
100352065  interleukin-23 subunit alpha [KO:K05426]
127487391  interleukin-23 subunit alpha-like [KO:K05426]
100350416  interleukin-12 receptor subunit beta-2 [KO:K05064]
100350917  interleukin-23 receptor [KO:K05065]
100008786  EPO; erythropoietin precursor [KO:K05437]
100356068  somatotropin precursor [KO:K05438]
100009394  PRL; prolactin precursor [KO:K05439]
100357079  thrombopoietin isoform X1 [KO:K06854]
100356652  granulocyte colony-stimulating factor [KO:K05423]
100008747  LEP; leptin precursor [KO:K05424]
100355350  erythropoietin receptor [KO:K05079]
100009325  GHR; growth hormone receptor precursor [KO:K05080]
100009046  PRLR; prolactin receptor precursor [KO:K05081]
100355135  thrombopoietin receptor [KO:K05082]
100342746  LOW QUALITY PROTEIN: granulocyte colony-stimulating factor receptor [KO:K05061]
100351924  leptin receptor isoform X2 [KO:K05062]
100353390  interferon alpha-21-like [KO:K05414]
100354654  interferon alpha-21-like [KO:K05414]
100355669  interferon alpha-21-like [KO:K05414]
100355912  interferon alpha-5-like [KO:K05414]
100356419  interferon alpha-14-like [KO:K05414]
100356678  interferon alpha-1/13 [KO:K05414]
100357194  interferon alpha-21-like [KO:K05414]
100357708  interferon alpha-21-like isoform X2 [KO:K05414]
100342931  interferon beta [KO:K05415]
100341910  interferon epsilon [KO:K05442]
100348954  interferon kappa [KO:K05441]
100341420  interferon lambda-3-like [KO:K05447]
100353137  interferon omega-1-like [KO:K05440]
100353640  interferon omega-1-like [KO:K05440]
100353888  interferon omega-1-like [KO:K05440]
100354397  interferon omega-1 [KO:K05440]
100354910  interferon omega-1-like [KO:K05440]
100355421  interferon omega-1 [KO:K05440]
100357452  interferon omega-1-like [KO:K05440]
100358223  interferon omega-1 [KO:K05440]
100338604  interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
100338097  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
100356641  interferon lambda receptor 1 isoform X2 [KO:K05140]
100008602  IFNG; interferon gamma precursor [KO:K04687]
100341787  interferon gamma receptor 1 isoform X1 [KO:K05132]
100338854  interferon gamma receptor 2 [KO:K05133]
100008808  pro-epidermal growth factor [KO:K04357]
100352388  platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100358772  platelet-derived growth factor subunit B isoform X1 [KO:K17386]
100008806  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100343006  platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
100342872  platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
100352594  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100358134  tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
127486194  tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
100344622  non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
100343893  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
127488928  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100344467  signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
127491150  LOW QUALITY PROTEIN: signal transducer and activator of transcription 2-like [KO:K11221]
100348778  signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
100344146  signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
127488925  signal transducer and activator of transcription 4-like [KO:K11222]
100348518  signal transducer and activator of transcription 5A [KO:K11223]
100348267  signal transducer and activator of transcription 5B [KO:K11224]
100344264  signal transducer and activator of transcription 6 [KO:K11225]
100344432  interferon regulatory factor 9 isoform X2 [KO:K04693]
100341861  cytokine-inducible SH2-containing protein isoform X1 [KO:K04701]
100339386  suppressor of cytokine signaling 1 [KO:K04694]
100354019  suppressor of cytokine signaling 2 [KO:K04695]
103346588  suppressor of cytokine signaling 3 [KO:K04696]
100357417  suppressor of cytokine signaling 4 [KO:K04697]
100353407  suppressor of cytokine signaling 5 [KO:K04698]
100344911  suppressor of cytokine signaling 6 [KO:K04699]
100351533  suppressor of cytokine signaling 7 isoform X1 [KO:K04699]
103349397  apoptosis regulator Bcl-2 [KO:K02161]
100359222  induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
100008875  BCL2L1; bcl-2-like protein 1 [KO:K04570]
100342639  serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100009036  G1/S-specific cyclin-D2 [KO:K10151]
100009038  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100348489  cyclin-dependent kinase inhibitor 1 [KO:K06625]
100008601  AOX1; aldehyde oxidase 1 [KO:K00157] [EC:1.2.3.1]
100345417  AOX2; aldehyde oxidase 2 [KO:K00157] [EC:1.2.3.1]
100345675  AOX3; aldehyde oxidase 3 [KO:K00157] [EC:1.2.3.1]
100354428  AOX4; aldehyde oxidase 4 [KO:K00157] [EC:1.2.3.1]
127485684  aldehyde oxidase 3-like [KO:K00157] [EC:1.2.3.1]
127491577  aldehyde oxidase 1-like [KO:K00157] [EC:1.2.3.1]
100352532  glial fibrillary acidic protein isoform X1 [KO:K05640]
100346128  signal transducing adapter molecule 1 isoform X1 [KO:K04705]
100351322  signal transducing adapter molecule 2 isoform X1 [KO:K04705]
100338151  tyrosine-protein phosphatase non-receptor type 2 isoform X4 [KO:K18026] [EC:3.1.3.48]
100348648  tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
100340619  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100354135  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100339509  E3 SUMO-protein ligase PIAS1 isoform X2 [KO:K04706] [EC:2.3.2.-]
100357839  E3 SUMO-protein ligase PIAS2 isoform X1 [KO:K16063] [EC:2.3.2.-]
100341019  E3 SUMO-protein ligase PIAS3 isoform X1 [KO:K16064] [EC:2.3.2.-]
100357263  four and a half LIM domains protein 1 isoform X5 [KO:K14365]
100339517  tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100342500  growth factor receptor-bound protein 2 [KO:K04364]
100346391  son of sevenless homolog 2 isoform X1 [KO:K03099]
100356615  son of sevenless homolog 1 isoform X1 [KO:K03099]
127486605  GTPase HRas isoform X1 [KO:K02833]
100347407  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100337822  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100345181  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100348663  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100345250  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100357841  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100342852  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100353706  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127486116  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100356164  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
ocu04010  MAPK signaling pathway
ocu04060  Cytokine-cytokine receptor interaction
ocu04110  Cell cycle
ocu04120  Ubiquitin mediated proteolysis
ocu04151  PI3K-Akt signaling pathway
ocu04210  Apoptosis
KO pathway
ko04630   
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