KEGG   PATHWAY: pale04630
pale04630                   Pathway                                

JAK-STAT signaling pathway - Pteropus alecto (black flying fox)
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.
Environmental Information Processing; Signal transduction
Pathway map
pale04630  JAK-STAT signaling pathway

Other DBs
GO: 0007259
Pteropus alecto (black flying fox) [GN:pale]
102895516  IL2; interleukin-2 [KO:K05429]
102896574  interleukin-3 [KO:K04736]
102890025  IL4; interleukin-4 [KO:K05430]
102890771  IL5; interleukin-5 [KO:K05428]
102895746  IL6; interleukin-6 [KO:K05405]
112472586  IL7; interleukin-7 [KO:K05431]
102894278  IL9; interleukin-9 [KO:K05432]
102887289  IL10; interleukin-10 [KO:K05443]
102887342  IL11; interleukin-11 isoform X2 [KO:K05417]
102887571  IL12A; interleukin-12 subunit alpha [KO:K05406]
102884214  IL12B; interleukin-12 subunit beta [KO:K05425]
102890275  IL13; interleukin-13 [KO:K05435]
102887558  IL15; interleukin-15 isoform X2 [KO:K05433]
102887033  IL19; interleukin-19 [KO:K05444]
102886783  IL20; interleukin-20 [KO:K22667]
102895772  IL21; interleukin-21 [KO:K05434]
102882933  IL22; interleukin-22 [KO:K05445]
102879394  IL23A; interleukin-23 subunit alpha [KO:K05426]
102886533  IL24; interleukin-24 [KO:K22668]
102893886  interferon alpha-1 [KO:K05414]
102890009  interferon alpha-4 [KO:K05414]
102890512  IFNB1; interferon beta [KO:K05415]
102882436  IFNG; interferon gamma precursor [KO:K04687]
102893643  IFNE; interferon epsilon [KO:K05442]
102889993  IFNK; interferon kappa [KO:K05441]
102894035  IFNL1; interferon lambda-1 precursor [KO:K05447]
102889807  interferon lambda-3-like [KO:K22669]
102889565  interferon lambda-3-like [KO:K22669]
102894127  interferon omega-2 [KO:K05440]
102882571  interferon omega-1 [KO:K05440]
102880610  LOW QUALITY PROTEIN: interferon omega-1-like [KO:K05440]
102896930  interferon omega-2-like [KO:K05440]
102889450  OSM; oncostatin-M [KO:K05418]
102889191  LIF; leukemia inhibitory factor isoform X1 [KO:K05419]
102896947  TSLP; thymic stromal lymphopoietin [KO:K05436]
102889242  CTF1; cardiotrophin-1 [KO:K05422]
102889489  cardiotrophin-2 [KO:K24382]
102893042  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
102895952  CNTF; ciliary neurotrophic factor [KO:K05420]
102882020  CSF3; granulocyte colony-stimulating factor isoform X1 [KO:K05423]
102883166  EPO; erythropoietin [KO:K05437]
102888823  somatotropin [KO:K05438]
102896937  LEP; leptin [KO:K05424]
102878621  THPO; thrombopoietin [KO:K06854]
102887064  PRL; prolactin isoform X1 [KO:K05439]
102891552  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102893670  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
102897699  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
102891511  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
102883396  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
102888070  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
102878242  IL3RA; interleukin-3 receptor subunit alpha [KO:K04737]
102882815  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
102896000  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
102878027  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
102889092  IL7R; interleukin-7 receptor subunit alpha [KO:K05072]
102883479  LOW QUALITY PROTEIN: interleukin-9 receptor [KO:K05073]
102890810  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
102899031  IL10RB; interleukin-10 receptor subunit beta precursor [KO:K05135]
102892445  IL11RA; interleukin-11 receptor subunit alpha isoform X4 [KO:K05056]
102878946  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
102885605  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
102897874  IL13RA1; interleukin-13 receptor subunit alpha-1 [KO:K05076]
102889724  IL13RA2; interleukin-13 receptor subunit alpha-2 [KO:K05077]
102892156  IL15RA; interleukin-15 receptor subunit alpha [KO:K05074]
102888258  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
102882035  IL20RB; interleukin-20 receptor subunit beta isoform X1 [KO:K05137]
102883062  IL21R; interleukin-21 receptor [KO:K05075]
102879965  IL22RA1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
102879846  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
102885363  IL23R; interleukin-23 receptor [KO:K05065]
102893026  IL27RA; LOW QUALITY PROTEIN: interleukin-27 receptor subunit alpha [KO:K19598]
102880415  IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060]
102892040  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
102891485  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
102888010  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102877930  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102879707  IFNLR1; interferon lambda receptor 1 precursor [KO:K05140]
102884525  OSMR; oncostatin-M-specific receptor subunit beta isoform X1 [KO:K05057]
102884262  LIFR; leukemia inhibitory factor receptor isoform X1 [KO:K05058]
102878749  CRLF2; cytokine receptor-like factor 2 [KO:K05078]
102894001  CNTFR; ciliary neurotrophic factor receptor subunit alpha [KO:K05059]
102878494  granulocyte-macrophage colony-stimulating factor receptor subunit alpha [KO:K05066]
102897194  CSF2RB; cytokine receptor common subunit beta [KO:K04738]
102897878  CSF3R; granulocyte colony-stimulating factor receptor isoform X1 [KO:K05061]
102886625  EPOR; erythropoietin receptor [KO:K05079]
102891638  GHR; growth hormone receptor [KO:K05080]
102882664  LEPR; leptin receptor [KO:K05062]
102880336  MPL; thrombopoietin receptor [KO:K05082]
102890093  PRLR; prolactin receptor [KO:K05081]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
102895362  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:]
102887643  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:]
102880365  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:]
102882079  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:]
102898620  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:]
102895629  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:]
102886603  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
102879640  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102884374  STAT3; LOW QUALITY PROTEIN: signal transducer and activator of transcription 3 [KO:K04692]
102886854  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102884638  signal transducer and activator of transcription 5A [KO:K11223]
102884882  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
102885160  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
102881891  CISH; cytokine-inducible SH2-containing protein [KO:K04701]
102878735  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
102889529  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
102887834  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102879275  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
102895579  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
102893297  SOCS7; suppressor of cytokine signaling 7 isoform X2 [KO:K04699]
102888661  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
102896443  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102884014  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
102887704  BCL2L1; bcl-2-like protein 1 [KO:K04570]
102891826  PIM1; serine/threonine-protein kinase pim-1 [KO:K04702] [EC:]
102895524  MYC; myc proto-oncogene protein [KO:K04377]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102892640  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102881884  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102895358  aldehyde oxidase 2 [KO:K00157] [EC:]
102879869  LOW QUALITY PROTEIN: aldehyde oxidase 4-like [KO:K00157] [EC:]
102895484  GFAP; glial fibrillary acidic protein isoform X1 [KO:K05640]
102880226  STAM; signal transducing adapter molecule 1 [KO:K04705]
102897126  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
102880076  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X1 [KO:K18026] [EC:]
102895931  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:]
102894320  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
102886172  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:]
102881042  EP300; histone acetyltransferase p300 [KO:K04498] [EC:]
102893358  PIAS1; E3 SUMO-protein ligase PIAS1 isoform X1 [KO:K04706] [EC:2.3.2.-]
102895265  PIAS2; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS2 [KO:K16063] [EC:2.3.2.-]
102895609  PIAS3; E3 SUMO-protein ligase PIAS3 [KO:K16064] [EC:2.3.2.-]
102893203  PIAS4; E3 SUMO-protein ligase PIAS4 [KO:K16065] [EC:]
102879672  FHL1; four and a half LIM domains protein 1 isoform X2 [KO:K14365]
102889219  PTPN11; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
102885092  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:]
Harrison DA
The Jak/STAT pathway.
Cold Spring Harb Perspect Biol 4:a011205 (2012)
Kiu H, Nicholson SE
Biology and significance of the JAK/STAT signalling pathways.
Growth Factors 30:88-106 (2012)
Hervas-Stubbs S, Perez-Gracia JL, Rouzaut A, Sanmamed MF, Le Bon A, Melero I
Direct effects of type I interferons on cells of the immune system.
Clin Cancer Res 17:2619-27 (2011)
Fish EN, Platanias LC
Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes.
Mol Cancer Res 12:1691-703 (2014)
Ivanenkov YA, Balakin KV, Lavrovsky Y
Small molecule inhibitors of NF-kB and JAK/STAT signal transduction pathways as promising anti-inflammatory therapeutics.
Mini Rev Med Chem 11:55-78 (2011)
O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A
The JAK-STAT pathway: impact on human disease and therapeutic intervention.
Annu Rev Med 66:311-28 (2015)
Zoranovic T, Grmai L, Bach EA
Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway.
JAKSTAT 2:e25408 (2013)
Ungureanu D, Silvennoinen O
SLIM trims STATs: ubiquitin E3 ligases provide insights for specificity in the regulation of cytokine signaling.
Sci STKE 2005:pe49 (2005)
Richard AJ, Stephens JM
The role of JAK-STAT signaling in adipose tissue function.
Biochim Biophys Acta 1842:431-9 (2014)
Sun Y, Lehmbecker A, Kalkuhl A, Deschl U, Sun W, Rohn K, Tzvetanova ID, Nave KA, Baumgartner W, Ulrich R
STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler's murine encephalomyelitis.
Neuropathol Appl Neurobiol 41:347-70 (2015)
Hirano T, Ishihara K, Hibi M
Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
Oncogene 19:2548-56 (2000)
Rane SG, Reddy EP
Janus kinases: components of multiple signaling pathways.
Oncogene 19:5662-79 (2000)
Heim MH
The Jak-STAT pathway: specific signal transduction from the cell membrane to the nucleus.
Eur J Clin Invest 26:1-12 (1996)
pale04010  MAPK signaling pathway
pale04060  Cytokine-cytokine receptor interaction
pale04110  Cell cycle
pale04120  Ubiquitin mediated proteolysis
pale04151  PI3K-Akt signaling pathway
pale04210  Apoptosis
KO pathway

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