KEGG   PATHWAY: rno04630
Entry
rno04630                    Pathway                                
Name
JAK-STAT signaling pathway - Rattus norvegicus (rat)
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
rno04630  JAK-STAT signaling pathway
rno04630

Other DBs
GO: 0007259
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
116562  Il2; interleukin-2 precursor [KO:K05429]
287287  Il4; interleukin-4 precursor [KO:K05430]
25647  Il7; interleukin-7 precursor [KO:K05431]
116558  Il9; interleukin-9 precursor [KO:K05432]
25670  Il15; interleukin-15 preproprotein [KO:K05433]
365769  Il21; interleukin-21 precursor [KO:K05434]
688621  Tslp; thymic stromal lymphopoietin isoform X1 [KO:K05436]
25704  Il2ra; interleukin-2 receptor subunit alpha precursor [KO:K05068]
25746  Il2rb; interleukin-2 receptor subunit beta precursor [KO:K05069]
140924  Il2rg; cytokine receptor common subunit gamma precursor [KO:K05070]
25084  Il4r; interleukin-4 receptor subunit alpha precursor [KO:K05071]
294797  Il7r; interleukin-7 receptor subunit alpha precursor [KO:K05072]
24500  Il9r; interleukin-9 receptor [KO:K05073]
690369  Il15ra; interleukin-15 receptor subunit alpha precursor [KO:K05074]
308977  Il21r; interleukin-21 receptor precursor [KO:K05075]
171499  Crlf2; cytokine receptor-like factor 2 precursor [KO:K05078]
24495  Il3; interleukin-3 precursor [KO:K04736]
24497  Il5; interleukin-5 precursor [KO:K05428]
116630  Csf2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
246144  Il3ra; interleukin-3 receptor subunit alpha precursor [KO:K04737]
114103  Il5ra; interleukin-5 receptor subunit alpha precursor [KO:K05067]
652957  Csf2ra; granulocyte-macrophage colony-stimulating factor receptor subunit alpha precursor [KO:K05066]
171081  Csf2rb; cytokine receptor common subunit beta precursor [KO:K04738]
24498  Il6; interleukin-6 precursor [KO:K05405]
171040  Il11; interleukin-11 precursor [KO:K05417]
116553  Il13; interleukin-13 precursor [KO:K05435]
365368  Il27; interleukin-27 subunit alpha [KO:K22629]
690028  Il31; interleukin-31 [KO:K22631]
289747  Osm; oncostatin-M precursor [KO:K05418]
60584  Lif; leukemia inhibitory factor precursor [KO:K05419]
25707  Cntf; ciliary neurotrophic factor [KO:K05420]
29201  Ctf1; cardiotrophin-1 [KO:K05422]
293515  Ctf2; cardiotrophin-2 precursor [KO:K24382]
365395  Clcf1; cardiotrophin-like cytokine factor 1 isoform 1 precursor [KO:K05421]
24499  Il6r; interleukin-6 receptor subunit alpha precursor [KO:K05055]
25205  Il6st; interleukin-6 receptor subunit beta precursor [KO:K05060]
245983  Il11ra1; interleukin-11 receptor subunit alpha precursor [KO:K05056]
252963  Il13ra1; interleukin-13 receptor subunit alpha-1 precursor [KO:K05076]
171060  Il13ra2; interleukin-13 receptor subunit alpha-2 precursor [KO:K05077]
688622  Il31ra; interleukin-31 receptor subunit alpha precursor [KO:K22630]
310132  Osmr; oncostatin-M-specific receptor subunit beta precursor [KO:K05057]
81680  Lifr; leukemia inhibitory factor receptor precursor [KO:K05058]
313173  Cntfr; ciliary neurotrophic factor receptor subunit alpha precursor [KO:K05059]
25325  Il10; interleukin-10 precursor [KO:K05443]
681145  Il19; interleukin-19 [KO:K05444]
500836  Il22; interleukin-22 precursor [KO:K05445]
681112  Il20; interleukin-20 [KO:K22667]
170819  Il24; interleukin-24 precursor [KO:K22668]
117539  Il10ra; interleukin-10 receptor subunit alpha precursor [KO:K05134]
304091  Il10rb; interleukin-10 receptor subunit beta precursor [KO:K05135]
308716  Il20ra; interleukin-20 receptor subunit alpha precursor [KO:K05136]
501043  Il20rb; interleukin-20 receptor subunit beta [KO:K05137]
362629  Il22ra1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
444986  Il22ra2; interleukin-22 receptor subunit alpha-2 precursor [KO:K05139]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
155140  Il23a; interleukin-23 subunit alpha precursor [KO:K05426]
171333  Il12rb1; interleukin-12 receptor subunit beta-1 precursor [KO:K05063]
171334  Il12rb2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
689932  Il23r; interleukin-23 receptor isoform X1 [KO:K05065]
24335  Epo; erythropoietin precursor [KO:K05437]
24391  Gh1; somatotropin precursor [KO:K05438]
24683  Prl; prolactin precursor [KO:K05439]
24657  Prl6a1; prolactin-6A1 precursor [KO:K05439]
171556  Prl5a1; prolactin-5A1 precursor [KO:K05439]
81811  Thpol1; thrombopoietin precursor [KO:K06854]
25610  Csf3; granulocyte colony-stimulating factor precursor [KO:K05423]
25608  Lep; leptin precursor [KO:K05424]
24336  Epor; erythropoietin receptor precursor [KO:K05079]
25235  Ghr; growth hormone receptor precursor [KO:K05080]
24684  Prlr; prolactin receptor isoform a precursor [KO:K05081]
366455  Mpl; thrombopoietin receptor precursor [KO:K05082]
298518  Csf3r; granulocyte colony-stimulating factor receptor precursor [KO:K05061]
24536  Lepr; leptin receptor precursor [KO:K05062]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha family, gene 5 precursor [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  Ifna4l2; similar to Interferon alpha-1 precursor [KO:K05414]
500491  Ifna16l1; interferon, alpha 16-like 1 precursor [KO:K05414]
134487075  interferon alpha-1-like [KO:K05414]
134487077  interferon alpha-1-like [KO:K05414]
100911527  Ifna4l1; interferon alpha-11-like [KO:K05414]
100912356  interferon alpha-1-like precursor [KO:K05414]
502959  Ifna1l1; similar to put. precursor MuIFN-alpha 5 precursor [KO:K05414]
24481  Ifnb1; interferon beta precursor [KO:K05415]
313152  Ifnk; interferon kappa precursor [KO:K05441]
100911249  Ifnl1; interferon lambda-2 [KO:K22669]
685840  Ifnl3; interferon lambda-2 [KO:K22669]
288264  Ifnar1; interferon alpha/beta receptor 1 isoform 1 precursor [KO:K05130]
686326  Ifnar2; interferon alpha and beta receptor subunit 2 isoform 1 precursor [KO:K05131]
362628  Ifnlr1; interferon lambda receptor 1 precursor [KO:K05140]
25712  Ifng; interferon gamma precursor [KO:K04687]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
25313  Egf; pro-epidermal growth factor precursor [KO:K04357]
25266  Pdgfa; platelet-derived growth factor subunit A precursor [KO:K04359]
24628  Pdgfb; platelet-derived growth factor subunit B precursor [KO:K17386]
24329  Egfr; epidermal growth factor receptor isoform 2 precursor [KO:K04361] [EC:2.7.10.1]
25267  Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363] [EC:2.7.10.1]
24629  Pdgfrb; platelet-derived growth factor receptor beta precursor [KO:K05089] [EC:2.7.10.1]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
25326  Jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
25125  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
367264  Stat4; signal transducer and activator of transcription 4 [KO:K11222]
24918  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
25126  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
362896  Stat6; signal transducer and activator of transcription 6 [KO:K11225]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
83681  Cish; cytokine-inducible SH2-containing protein [KO:K04701]
252971  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
84607  Socs2; suppressor of cytokine signaling 2 [KO:K04695]
89829  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
305828  Socs4; suppressor of cytokine signaling 4 [KO:K04697]
500616  Socs5; suppressor of cytokine signaling 5 [KO:K04698]
287659  Socs7; suppressor of cytokine signaling 7 [KO:K04699]
307200  Socs6; suppressor of cytokine signaling 6 [KO:K04699]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
60430  Mcl1; induced myeloid leukemia cell differentiation protein Mcl-1 homolog [KO:K02539]
24888  Bcl2l1; bcl-2-like protein 1 isoform 2 [KO:K04570]
24649  Pim1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
24577  Myc; myc proto-oncogene protein [KO:K04377]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
64033  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
25193  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
114851  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
54349  Aox1; aldehyde oxidase 1 [KO:K00157] [EC:1.2.3.1]
316421  Aox2; aldehyde oxidase 2 [KO:K00157] [EC:1.2.3.1]
493909  Aox3; aldehyde oxidase 3 [KO:K00157] [EC:1.2.3.1]
316424  Aox4; aldehyde oxidase 4 [KO:K00157] [EC:1.2.3.1]
24387  Gfap; glial fibrillary acidic protein [KO:K05640]
311030  Stam2; signal transducing adapter molecule 2 [KO:K04705]
498798  Stam; signal transducing adapter molecule 1 [KO:K04705]
117063  Ptpn2; tyrosine-protein phosphatase non-receptor type 2 isoform 1 [KO:K18026] [EC:3.1.3.48]
116689  Ptpn6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
54244  Crebbp; histone lysine acetyltransferase CREBBP [KO:K04498] [EC:2.3.1.48]
170915  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
300772  Pias1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
83422  Pias2; E3 SUMO-protein ligase PIAS2 isoform 2 [KO:K16063] [EC:2.3.2.-]
83614  Pias3; E3 SUMO-protein ligase PIAS3 [KO:K16064] [EC:2.3.2.-]
362827  Pias4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
25177  Fhl1; four and a half LIM domains protein 1 isoform 3 [KO:K14365]
25622  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform 2 [KO:K07293] [EC:3.1.3.48]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
56718  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
rno04010  MAPK signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04110  Cell cycle
rno04120  Ubiquitin mediated proteolysis
rno04151  PI3K-Akt signaling pathway
rno04210  Apoptosis
KO pathway
ko04630   
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