KEGG   PATHWAY: hgl04630
Entry
hgl04630                    Pathway                                
Name
JAK-STAT signaling pathway - Heterocephalus glaber (naked mole-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
hgl04630  JAK-STAT signaling pathway
hgl04630

Other DBs
GO: 0007259
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101720581  Il2; interleukin 2 [KO:K05429]
101706414  Il4; interleukin 4 [KO:K05430]
101713773  Il7; interleukin 7 [KO:K05431]
101713016  Il9; interleukin 9 [KO:K05432]
101718208  Il15; interleukin 15 [KO:K05433]
101720915  Il21; interleukin 21 [KO:K05434]
101696651  Il2ra; interleukin 2 receptor subunit alpha [KO:K05068]
101726369  Il2rb; interleukin 2 receptor subunit beta [KO:K05069]
101715243  Il2rg; interleukin 2 receptor subunit gamma [KO:K05070]
101704138  Il4r; interleukin 4 receptor [KO:K05071]
101710077  Il7r; interleukin 7 receptor [KO:K05072]
101723734  Il9r; interleukin 9 receptor [KO:K05073]
101721276  Il15ra; interleukin 15 receptor subunit alpha [KO:K05074]
101701307  Il21r; interleukin 21 receptor [KO:K05075]
101702063  Crlf2; cytokine receptor-like factor 2 [KO:K05078]
101719528  Il5; interleukin 5 [KO:K05428]
101724943  Csf2; colony stimulating factor 2 [KO:K05427]
101696721  Il3ra; interleukin 3 receptor subunit alpha [KO:K04737]
101701153  Il5ra; interleukin 5 receptor subunit alpha [KO:K05067]
101702638  granulocyte-macrophage colony-stimulating factor receptor subunit alpha-like [KO:K05066]
101698831  Csf2rb; cytokine receptor common subunit beta [KO:K04738]
101698455  cytokine receptor common subunit beta-like [KO:K04738]
101702602  Il6; interleukin 6 [KO:K05405]
101706608  Il11; interleukin 11 [KO:K05417]
101718152  Il13; interleukin 13 [KO:K05435]
101724119  Il27; interleukin 27 [KO:K22629]
101697067  Il31; interleukin 31 [KO:K22631]
101705496  Osm; oncostatin M [KO:K05418]
101713065  Lif; leukemia inhibitory factor [KO:K05419]
101713822  Cntf; ciliary neurotrophic factor [KO:K05420]
101703771  Ctf1; cardiotrophin 1 [KO:K05422]
101704388  cardiotrophin-2 [KO:K24382]
101706033  Clcf1; cardiotrophin-like cytokine factor 1 [KO:K05421]
101704925  Il6r; interleukin 6 receptor [KO:K05055]
101703833  Il6st; interleukin 6 signal transducer [KO:K05060]
101708949  Il11ra; interleukin 11 receptor subunit alpha [KO:K05056]
101723721  Il13ra1; interleukin 13 receptor subunit alpha 1 [KO:K05076]
101725943  Il13ra2; interleukin 13 receptor subunit alpha 2 [KO:K05077]
101699944  Il27ra; interleukin 27 receptor subunit alpha [KO:K19598]
101704202  Il31ra; interleukin 31 receptor A [KO:K22630]
101696496  Osmr; oncostatin M receptor [KO:K05057]
101696861  Lifr; leukemia inhibitory factor receptor alpha [KO:K05058]
101704145  Cntfr; ciliary neurotrophic factor receptor [KO:K05059]
101708273  Il10; interleukin 10 [KO:K05443]
101725985  Il19; interleukin 19 [KO:K05444]
101700360  Il22; interleukin 22 [KO:K05445]
101707909  Il20; interleukin 20 [KO:K22667]
101707178  Il24; interleukin 24 [KO:K22668]
101706700  Il26; interleukin 26 [KO:K05446]
101706532  Il10ra; interleukin 10 receptor subunit alpha [KO:K05134]
101723546  Il10rb; interleukin 10 receptor subunit beta [KO:K05135]
101699117  Il20ra; interleukin 20 receptor subunit alpha [KO:K05136]
101721740  Il20rb; interleukin 20 receptor subunit beta [KO:K05137]
101721365  Il22ra1; interleukin 22 receptor subunit alpha 1 [KO:K05138]
101698371  Il22ra2; interleukin 22 receptor subunit alpha 2 [KO:K05139]
101701392  Il12a; interleukin 12A [KO:K05406]
101701309  Il12b; interleukin 12B [KO:K05425]
101707902  Il23a; interleukin 23 subunit alpha [KO:K05426]
101702338  Il12rb1; interleukin 12 receptor subunit beta 1 [KO:K05063]
101717608  Il12rb2; interleukin 12 receptor subunit beta 2 [KO:K05064]
101697943  Il23r; interleukin 23 receptor [KO:K05065]
101712254  Gh1; growth hormone 1 [KO:K05438]
106009625  prolactin-like [KO:K05439]
101699327  prolactin-like [KO:K05439]
101696723  Prl; prolactin [KO:K05439]
101705058  Thpo; thrombopoietin [KO:K06854]
101698554  Csf3; colony stimulating factor 3 [KO:K05423]
101722703  Lep; leptin [KO:K05424]
101710668  Epor; erythropoietin receptor [KO:K05079]
101716037  Ghr; growth hormone receptor [KO:K05080]
101707597  Mpl; MPL proto-oncogene, thrombopoietin receptor [KO:K05082]
101723599  Csf3r; colony stimulating factor 3 receptor [KO:K05061]
101705981  Lepr; leptin receptor [KO:K05062]
101697163  interferon alpha-4-like [KO:K05414]
101699042  Ifnb1; interferon beta 1 [KO:K05415]
101723869  interferon beta-like [KO:K05415]
101699626  Ifne; interferon epsilon [KO:K05442]
101706424  Ifnk; interferon kappa [KO:K05441]
101699159  Ifnl2; interferon lambda-2 [KO:K22669]
101719419  interferon lambda-2 [KO:K22669]
101697684  Ifnl3; interferon lambda 3 [KO:K22669]
101698799  interferon lambda-2-like [KO:K22669]
101724158  Ifnar1; interferon alpha and beta receptor subunit 1 [KO:K05130]
101722391  Ifnar2; interferon alpha and beta receptor subunit 2 [KO:K05131]
101698624  Ifnlr1; interferon lambda receptor 1 [KO:K05140]
101700722  Ifng; interferon gamma [KO:K04687]
101709169  Ifngr1; interferon gamma receptor 1 [KO:K05132]
101724858  Ifngr2; interferon gamma receptor 2 [KO:K05133]
106007527  Egf; epidermal growth factor [KO:K04357]
101725739  Pdgfa; platelet derived growth factor subunit A [KO:K04359]
101698830  Pdgfb; platelet derived growth factor subunit B [KO:K17386]
101723771  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
101697360  Pdgfra; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
101721151  Pdgfrb; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
101710283  Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
101717708  Jak2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
101715472  Jak3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
101715782  Tyk2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
101718902  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
101707295  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
101721899  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
101718558  Stat4; signal transducer and activator of transcription 4 [KO:K11222]
101722721  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
101725744  Stat6; signal transducer and activator of transcription 6 [KO:K11225]
101701338  Irf9; interferon regulatory factor 9 [KO:K04693]
101716746  Cish; cytokine inducible SH2 containing protein [KO:K04701]
101723330  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
101716580  Socs2; suppressor of cytokine signaling 2 [KO:K04695]
101704157  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
101704725  Socs4; suppressor of cytokine signaling 4 [KO:K04697]
101703084  Socs5; suppressor of cytokine signaling 5 [KO:K04698]
101716336  Socs6; suppressor of cytokine signaling 6 [KO:K04699]
101725097  Socs7; suppressor of cytokine signaling 7 [KO:K04699]
101706091  suppressor of cytokine signaling 6 [KO:K04699]
101701667  Bcl2; BCL2, apoptosis regulator [KO:K02161]
101724340  Mcl1; BCL2 family apoptosis regulator [KO:K02539]
101713410  Bcl2l1; BCL2 like 1 [KO:K04570]
101720105  bcl-2-like protein 1 [KO:K04570]
101706236  Pim1; Pim-1 proto-oncogene, serine/threonine kinase [KO:K04702] [EC:2.7.11.1]
101704740  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
101712621  Ccnd1; cyclin D1 [KO:K04503]
101721480  Ccnd2; cyclin D2 [KO:K10151]
101708062  Ccnd3; cyclin D3 [KO:K10152]
101710552  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
101710340  aldehyde oxidase 2-like [KO:K00157] [EC:1.2.3.1]
101722324  Aox4; aldehyde oxidase-like [KO:K00157] [EC:1.2.3.1]
101722898  Aox1; aldehyde oxidase 1 [KO:K00157] [EC:1.2.3.1]
101707892  Gfap; glial fibrillary acidic protein [KO:K05640]
101717932  Stam; signal transducing adaptor molecule [KO:K04705]
101722782  Stam2; signal transducing adaptor molecule 2 [KO:K04705]
101723984  signal transducing adapter molecule 2-like [KO:K04705]
101725549  Ptpn2; protein tyrosine phosphatase, non-receptor type 2 [KO:K18026] [EC:3.1.3.48]
101725029  Ptpn6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
101711512  Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
101714025  Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
101709056  Pias1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
101709303  Pias2; protein inhibitor of activated STAT 2 [KO:K16063] [EC:2.3.2.-]
101699952  Pias3; protein inhibitor of activated STAT 3 [KO:K16064] [EC:2.3.2.-]
101708989  Pias4; protein inhibitor of activated STAT 4 [KO:K16065] [EC:2.3.2.27]
101702039  Fhl1; four and a half LIM domains 1 [KO:K14365]
101701336  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
101717035  Grb2; growth factor receptor bound protein 2 [KO:K04364]
101707893  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
101701753  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
101716053  Hras; HRas proto-oncogene, GTPase [KO:K02833]
101721841  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
101711934  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
101715249  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
101712941  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
101718815  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
101717096  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101703691  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
101700695  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
101719164  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
101701289  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
101725626  Mtor; mechanistic target of rapamycin [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
hgl04010  MAPK signaling pathway
hgl04060  Cytokine-cytokine receptor interaction
hgl04110  Cell cycle
hgl04120  Ubiquitin mediated proteolysis
hgl04151  PI3K-Akt signaling pathway
hgl04210  Apoptosis
KO pathway
ko04630   
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