KEGG   PATHWAY: biu04630
Entry
biu04630                    Pathway                                
Name
JAK-STAT signaling pathway - Bos indicus (zebu cattle)
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
biu04630  JAK-STAT signaling pathway
biu04630

Other DBs
GO: 0007259
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109571028  IL2; interleukin-2 [KO:K05429]
109561213  IL4; interleukin-4 [KO:K05430]
109568650  IL7; interleukin-7 [KO:K05431]
109561070  IL9; interleukin-9 [KO:K05432]
109571474  IL15; interleukin-15 [KO:K05433]
109571034  IL21; interleukin-21 isoform X1 [KO:K05434]
109567961  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
109559534  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
109555190  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
109578521  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
109575020  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
109578826  interleukin-9 receptor-like [KO:K05073]
109567895  IL15RA; interleukin-15 receptor subunit alpha isoform X1 [KO:K05074]
109578841  IL21R; interleukin-21 receptor [KO:K05075]
109561219  interleukin-3 [KO:K04736]
109561216  IL5; interleukin-5 [KO:K05428]
109561218  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
109575848  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
109568669  LOW QUALITY PROTEIN: granulocyte-macrophage colony-stimulating factor receptor subunit alpha-like [KO:K05066]
109559524  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
109558077  IL6; interleukin-6 [KO:K05405]
109561215  IL13; interleukin-13 [KO:K05435]
109578638  IL27; interleukin-27 subunit alpha [KO:K22629]
109570838  OSM; oncostatin-M [KO:K05418]
109571543  LIF; leukemia inhibitory factor [KO:K05419]
109569574  CNTF; ciliary neurotrophic factor isoform X1 [KO:K05420]
109578719  CTF1; cardiotrophin-1 [KO:K05422]
109554138  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
109574817  IL6ST; interleukin-6 receptor subunit beta [KO:K05060]
109563195  IL11RA; interleukin-11 receptor subunit alpha [KO:K05056]
109560896  IL27RA; interleukin-27 receptor subunit alpha [KO:K19598]
109575060  IL31RA; interleukin-31 receptor subunit alpha [KO:K22630]
109574945  OSMR; oncostatin-M-specific receptor subunit beta [KO:K05057]
109574806  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
109563190  CNTFR; ciliary neurotrophic factor receptor subunit alpha [KO:K05059]
109570808  IL10; interleukin-10 [KO:K05443]
109570244  IL19; interleukin-19 [KO:K05444]
109558717  IL22; interleukin-22 [KO:K05445]
109570102  IL20; interleukin-20 [KO:K22667]
109570104  IL24; interleukin-24 [KO:K22668]
109558718  IL26; interleukin-26 [KO:K05446]
109569863  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
109571300  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
109563983  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
109560001  IL20RB; interleukin-20 receptor subunit beta [KO:K05137]
109577127  IL22RA1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
109563556  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
109564477  IL12A; interleukin-12 subunit alpha [KO:K05406]
109561305  IL12B; interleukin-12 subunit beta [KO:K05425]
109559359  IL23A; interleukin-23 subunit alpha [KO:K05426]
109561420  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
109556179  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
109556180  IL23R; interleukin-23 receptor isoform X1 [KO:K05065]
109578290  EPO; erythropoietin [KO:K05437]
109574543  somatotropin [KO:K05438]
109577452  placental prolactin-related protein 3-like [KO:K05439]
109577453  LOW QUALITY PROTEIN: placental prolactin-related protein 3-like [KO:K05439]
109576772  placental prolactin-related protein 1 isoform X1 [KO:K05439]
109576773  chorionic somatomammotropin hormone 2 [KO:K05439]
109576787  chorionic somatomammotropin hormone 1 isoform X1 [KO:K05439]
109576792  placental prolactin-related protein 4 [KO:K05439]
109576814  placental prolactin-related protein 3-like [KO:K05439]
109577296  prolactin [KO:K05439]
109576744  LOW QUALITY PROTEIN: chorionic somatomammotropin hormone 2-like [KO:K05439]
109557333  THPO; thrombopoietin isoform X1 [KO:K06854]
109573417  CSF3; granulocyte colony-stimulating factor isoform X1 [KO:K05423]
109557596  LEP; leptin isoform X1 [KO:K05424]
109561621  EPOR; erythropoietin receptor isoform X1 [KO:K05079]
109574810  GHR; growth hormone receptor isoform X1 [KO:K05080]
109574973  PRLR; prolactin receptor isoform X1 [KO:K05081]
109557096  MPL; thrombopoietin receptor [KO:K05082]
109556495  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
109556197  LEPR; leptin receptor [KO:K05062]
109562847  interferon alpha-H [KO:K05414]
109562638  interferon alpha-G-like [KO:K05414]
109562641  LOW QUALITY PROTEIN: interferon alpha-1-like [KO:K05414]
109562644  interferon alpha-F [KO:K05414]
109562652  interferon alpha-A [KO:K05414]
109562656  interferon alpha-H-like [KO:K05414]
109562659  interferon alpha-H-like [KO:K05414]
109562660  interferon alpha-H-like [KO:K05414]
109562665  interferon alpha-B-like [KO:K05414]
109562668  interferon alpha-2-like [KO:K05414]
109562670  interferon alpha-2-like [KO:K05414]
109562673  interferon alpha-3-like [KO:K05414]
109562852  interferon beta-2-like [KO:K05415]
109562853  interferon beta-1-like [KO:K05415]
109562855  interferon beta-1 [KO:K05415]
109562667  LOW QUALITY PROTEIN: interferon beta-3-like [KO:K05415]
109562671  interferon beta-2-like [KO:K05415]
109562674  interferon beta-2 [KO:K05415]
109562675  interferon beta-2-like [KO:K05415]
109562628  IFNE; interferon epsilon [KO:K05442]
109562827  IFNK; interferon kappa [KO:K05441]
109562844  interferon omega-1-like [KO:K05440]
109562846  interferon omega-1-like [KO:K05440]
109562848  interferon omega-1-like [KO:K05440]
109562634  interferon tau-3 [KO:K05440]
109562635  interferon omega-1 [KO:K05440]
109562636  interferon omega-1-like isoform X1 [KO:K05440]
109562637  interferon omega-1-like [KO:K05440]
109562640  interferon omega-1-like [KO:K05440]
109562642  interferon omega-1-like [KO:K05440]
109562643  interferon omega-1-like [KO:K05440]
109562645  interferon omega-1-like [KO:K05440]
109562646  interferon omega-1-like [KO:K05440]
109562647  interferon omega-1-like [KO:K05440]
109562651  interferon tau-1-like [KO:K05440]
109562653  LOW QUALITY PROTEIN: interferon omega-1-like [KO:K05440]
109562654  interferon omega-1-like [KO:K05440]
109562655  interferon omega-1-like [KO:K05440]
109562657  interferon omega-1-like [KO:K05440]
109562658  interferon omega-1-like [KO:K05440]
109562662  interferon omega-1-like [KO:K05440]
109562663  interferon omega-1-like [KO:K05440]
109562664  interferon omega-1-like [KO:K05440]
109562666  interferon omega-1-like [KO:K05440]
109570535  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
109572614  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
109573827  IFNLR1; interferon lambda receptor 1 [KO:K05140]
109558719  IFNG; interferon gamma [KO:K04687]
109563984  IFNGR1; interferon gamma receptor 1 [KO:K05132]
109569763  IFNGR2; interferon gamma receptor 2 [KO:K05133]
109559983  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
109578611  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
109558630  LOW QUALITY PROTEIN: platelet-derived growth factor subunit B-like [KO:K17386]
109559825  platelet-derived growth factor subunit B isoform X1 [KO:K17386]
109576048  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
109560475  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
109562197  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
109556202  JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
109562906  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
109561426  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
109561587  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
109568771  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
109559357  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
109573817  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
109575487  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
109574089  signal transducer and activator of transcription 5A-like [KO:K11223]
109573773  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
109559334  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
109564781  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
109576359  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
109578851  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
109558981  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
109574319  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
109565183  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
109566051  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
109577635  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
109573815  SOCS7; suppressor of cytokine signaling 7 isoform X1 [KO:K04699]
109577782  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109555382  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
109564155  induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
109567345  BCL2L1; bcl-2-like protein 1 [KO:K04570]
109565507  bcl-2-like protein 1 [KO:K04570]
109577351  PIM1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
109568594  MYC; myc proto-oncogene protein [KO:K04377]
109554439  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
109559745  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
109577151  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109577247  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
109569300  AOX1; aldehyde oxidase [KO:K00157] [EC:1.2.3.1]
109569310  aldehyde oxidase 4-like [KO:K00157] [EC:1.2.3.1]
109569328  aldehyde oxidase 2 [KO:K00157] [EC:1.2.3.1]
109574014  GFAP; glial fibrillary acidic protein isoform X1 [KO:K05640]
109567597  STAM2; LOW QUALITY PROTEIN: signal transducing adapter molecule 2 [KO:K04705]
109567984  STAM; signal transducing adapter molecule 1 isoform X1 [KO:K04705]
109577870  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:3.1.3.48]
109558908  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
109578349  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
109559852  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
109564711  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
109577794  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X1 [KO:K16063] [EC:2.3.2.-]
109555834  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X1 [KO:K16064] [EC:2.3.2.-]
109561754  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
109555079  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
109570927  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
109570168  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
109574040  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
109566002  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109564346  SOS2; son of sevenless homolog 2 [KO:K03099]
109560940  GTPase HRas-like [KO:K02833]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109572496  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109570286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109570401  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
biu04010  MAPK signaling pathway
biu04060  Cytokine-cytokine receptor interaction
biu04110  Cell cycle
biu04120  Ubiquitin mediated proteolysis
biu04151  PI3K-Akt signaling pathway
biu04210  Apoptosis
KO pathway
ko04630   
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