KEGG   PATHWAY: uah04630
Entry
uah04630                    Pathway                                
Name
JAK-STAT signaling pathway - Ursus arctos (brown bear)
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
uah04630  JAK-STAT signaling pathway
uah04630

Other DBs
GO: 0007259
Organism
Ursus arctos (brown bear) [GN:uah]
Gene
113240790  [KO:K04737]
113240792  [KO:K05066]
113240793  [KO:K05066]
113240794  [KO:K05078]
113240901  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
113241139  IL15RA; LOW QUALITY PROTEIN: interleukin-15 receptor subunit alpha [KO:K05074]
113241140  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
113241251  IL13RA2; interleukin-13 receptor subunit alpha-2 [KO:K05077]
113241264  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X1 [KO:K05076]
113241630  SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
113241737  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
113241764  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
113241866  FHL1; four and a half LIM domains protein 1 isoform X1 [KO:K14365]
113242351  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
113242440  IL19; interleukin-19 [KO:K05444]
113242441  IL20; interleukin-20 isoform X1 [KO:K22667]
113242596  IL10; interleukin-10 [KO:K05443]
113242598  IL24; interleukin-24 [KO:K22668]
113242820  PIAS4; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:2.3.2.27]
113242985  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X2 [KO:K11219] [EC:2.7.10.2]
113243022  EPOR; erythropoietin receptor [KO:K05079]
113243223  [KO:K05447]
113243255  [KO:K22669]
113243256  [KO:K22669]
113243572  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
113243982  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
113244034  CLCF1; cardiotrophin-like cytokine factor 1 isoform X2 [KO:K05421]
113244564  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
113244637  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
113245026  LIF; leukemia inhibitory factor isoform X2 [KO:K05419]
113245027  OSM; oncostatin-M [KO:K05418]
113245310  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
113245352  IL9R; interleukin-9 receptor isoform X1 [KO:K05073]
113245610  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
113245907  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X3 [KO:K18026] [EC:3.1.3.48]
113245987  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
113246066  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
113246198  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
113246400  CNTF; ciliary neurotrophic factor [KO:K05420]
113247162  IL27RA; interleukin-27 receptor subunit alpha isoform X2 [KO:K19598]
113247369  IL11; interleukin-11 [KO:K05417]
113247782  PIAS3; E3 SUMO-protein ligase PIAS3 isoform X1 [KO:K16064] [EC:2.3.2.-]
113249383  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
113249602  STAM; signal transducing adapter molecule 1 [KO:K04705]
113250605  [KO:K00157] [EC:1.2.3.1]
113250606  AOX1; aldehyde oxidase isoform X2 [KO:K00157] [EC:1.2.3.1]
113250607  [KO:K00157] [EC:1.2.3.1]
113250651  STAT4; signal transducer and activator of transcription 4 isoform X2 [KO:K11222]
113250654  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X2 [KO:K11220]
113250881  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
113252726  MYC; myc proto-oncogene protein [KO:K04377]
113253022  IL7; interleukin-7 [KO:K05431]
113253381  PIAS2; E3 SUMO-protein ligase PIAS2 isoform X1 [KO:K16063] [EC:2.3.2.-]
113253490  BCL2; apoptosis regulator Bcl-2 isoform X3 [KO:K02161]
113253516  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
113253976  IL20RB; interleukin-20 receptor subunit beta isoform X2 [KO:K05137]
113253989  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113254130  IL12A; interleukin-12 subunit alpha [KO:K05406]
113254294  THPO; LOW QUALITY PROTEIN: thrombopoietin [KO:K06854]
113254551  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
113254554  IL23R; interleukin-23 receptor [KO:K05065]
113254563  LEPR; leptin receptor isoform X1 [KO:K05062]
113254577  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
113254730  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
113254790  MPL; thrombopoietin receptor [KO:K05082]
113254799  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
113254959  TSLP; thymic stromal lymphopoietin [KO:K05436]
113255266  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
113255323  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
113255324  IL31RA; interleukin-31 receptor subunit alpha [KO:K22630]
113255465  IL21; interleukin-21 [KO:K05434]
113255562  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
113255635  IL2; interleukin-2 [KO:K05429]
113255706  IL15; interleukin-15 isoform X1 [KO:K05433]
113255914  IL22; interleukin-22 [KO:K05445]
113255915  IL26; interleukin-26 [KO:K05446]
113255980  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
113256161  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
113256304  IFNG; interferon gamma [KO:K04687]
113256394  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
113256419  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
113256421  IL23A; interleukin-23 subunit alpha isoform X1 [KO:K05426]
113256691  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
113256701  IL12RB1; LOW QUALITY PROTEIN: interleukin-12 receptor subunit beta-1 [KO:K05063]
113256705  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
113256921  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
113257099  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
113257190  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
113257444  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
113257950  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
113258003  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
113258218  [KO:K05447]
113258461  BCL2L1; bcl-2-like protein 1 [KO:K04570]
113259362  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
113259484  IL20RA; interleukin-20 receptor subunit alpha isoform X2 [KO:K05136]
113259485  IFNGR1; interferon gamma receptor 1 [KO:K05132]
113260009  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
113260289  IFNE; interferon epsilon [KO:K05442]
113260290  [KO:K05414]
113260291  [KO:K05414]
113260293  [KO:K05414]
113260294  [KO:K05414]
113260295  IFNB1; interferon beta [KO:K05415]
113260499  IL11RA; interleukin-11 receptor subunit alpha isoform X3 [KO:K05056]
113260507  CNTFR; ciliary neurotrophic factor receptor subunit alpha isoform X1 [KO:K05059]
113260554  IFNK; interferon kappa [KO:K05441]
113260881  PRLR; prolactin receptor isoform X1 [KO:K05081]
113260884  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
113260908  LIFR; leukemia inhibitory factor receptor isoform X2 [KO:K05058]
113260912  OSMR; oncostatin-M-specific receptor subunit beta isoform X3 [KO:K05057]
113260944  GHR; growth hormone receptor isoform X1 [KO:K05080]
113261280  IL6; interleukin-6 [KO:K05405]
113261302  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
113261494  IL9; interleukin-9 [KO:K05432]
113261702  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
113261704  [KO:K04736]
113261714  IL5; interleukin-5 [KO:K05428]
113261716  IL4; interleukin-4 [KO:K05430]
113262493  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
113262966  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113263750  LEP; leptin isoform X1 [KO:K05424]
113263879  IL12B; interleukin-12 subunit beta [KO:K05425]
113263944  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
113264523  PRL; prolactin isoform X2 [KO:K05439]
113264675  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
113264796  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
113264906  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
113265156  GH1; somatotropin [KO:K05438]
113265338  GFAP; glial fibrillary acidic protein isoform X1 [KO:K05640]
113265422  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
113265423  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
113265424  [KO:K11224]
113265548  SOCS7; suppressor of cytokine signaling 7 isoform X2 [KO:K04699]
113265687  CSF3; granulocyte colony-stimulating factor [KO:K05423]
113266205  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
113266983  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
113267111  IL31; interleukin-31 [KO:K22631]
113267192  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
113267511  [KO:K24382]
113267523  EPO; LOW QUALITY PROTEIN: erythropoietin [KO:K05437]
113267608  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
113267611  IL21R; interleukin-21 receptor [KO:K05075]
113267636  IL27; interleukin-27 subunit alpha [KO:K22629]
113267705  CTF1; cardiotrophin-1 [KO:K05422]
113268222  IFNLR1; interferon lambda receptor 1 [KO:K05140]
113268281  CSF3R; granulocyte colony-stimulating factor receptor [KO:K05061]
113268505  IL22RA1; LOW QUALITY PROTEIN: interleukin-22 receptor subunit alpha-1 [KO:K05138]
113270160  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
113270510  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
113270537  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
113270688  [KO:K07293] [EC:3.1.3.48]
113270798  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
113270858  CREBBP; CREB-binding protein isoform X3 [KO:K04498] [EC:2.3.1.48]
123000098  IL10RB; interleukin-10 receptor subunit beta isoform X1 [KO:K05135]
125282300  HRAS; GTPase HRas isoform X1 [KO:K02833]
125283239  [KO:K05414]
125283240  [KO:K05414]
125283241  [KO:K05414]
125283243  [KO:K05414]
125283244  [KO:K05414]
125283245  [KO:K05414]
125283246  [KO:K05414]
125283247  [KO:K05414]
125283248  [KO:K05414]
130541830  [KO:K05066]
130541834  [KO:K05066]
130544290  [KO:K05078]
130544379  [KO:K04737]
Reference
  Authors
Harrison DA
  Title
The Jak/STAT pathway.
  Journal
Cold Spring Harb Perspect Biol 4:a011205 (2012)
DOI:10.1101/cshperspect.a011205
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
uah04010  MAPK signaling pathway
uah04060  Cytokine-cytokine receptor interaction
uah04110  Cell cycle
uah04120  Ubiquitin mediated proteolysis
uah04151  PI3K-Akt signaling pathway
uah04210  Apoptosis
KO pathway
ko04630   

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