KEGG   PATHWAY: lav04630
Entry
lav04630                    Pathway                                
Name
JAK-STAT signaling pathway - Loxodonta africana (African savanna elephant)
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
lav04630  JAK-STAT signaling pathway
lav04630

Other DBs
GO: 0007259
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100656398  IL2; interleukin-2 [KO:K05429]
100674484  IL4; interleukin-4 [KO:K05430]
100658284  IL7; interleukin-7 [KO:K05431]
100666698  IL9; interleukin-9 [KO:K05432]
100657564  IL15; interleukin-15 [KO:K05433]
100656684  IL21; interleukin-21 [KO:K05434]
100670763  TSLP; LOW QUALITY PROTEIN: thymic stromal lymphopoietin [KO:K05436]
100655361  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
100669139  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
100664834  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
100654822  IL4R; interleukin-4 receptor subunit alpha [KO:K05071]
100671266  IL7R; interleukin-7 receptor subunit alpha isoform X1 [KO:K05072]
100654245  IL9R; interleukin-9 receptor isoform X1 [KO:K05073]
100655923  IL15RA; interleukin-15 receptor subunit alpha [KO:K05074]
100655109  IL21R; LOW QUALITY PROTEIN: interleukin-21 receptor [KO:K05075]
100663851  cytokine receptor-like factor 2 [KO:K05078]
111750521  interleukin-3-like [KO:K04736]
100663565  IL5; interleukin-5 [KO:K05428]
100675335  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
104847204  IL3RA; interleukin-3 receptor subunit alpha isoform X1 [KO:K04737]
100662380  IL5RA; interleukin-5 receptor subunit alpha [KO:K05067]
111749385  granulocyte-macrophage colony-stimulating factor receptor subunit alpha-like [KO:K05066]
100664139  CSF2RA; granulocyte-macrophage colony-stimulating factor receptor subunit alpha isoform X1 [KO:K05066]
100671503  cytokine receptor common subunit beta-like [KO:K04738]
100670281  cytokine receptor common subunit beta [KO:K04738]
100660846  IL6; interleukin-6 [KO:K05405]
100672413  IL11; interleukin-11 [KO:K05417]
100674770  IL13; interleukin-13 [KO:K05435]
100657097  IL27; interleukin-27 subunit alpha [KO:K22629]
104846894  IL31; interleukin-31 [KO:K22631]
100660616  OSM; oncostatin-M isoform X3 [KO:K05418]
100659089  LIF; leukemia inhibitory factor [KO:K05419]
100663082  leukemia inhibitory factor-like [KO:K05419]
100660906  leukemia inhibitory factor-like [KO:K05419]
100663365  leukemia inhibitory factor-like [KO:K05419]
100655202  leukemia inhibitory factor-like [KO:K05419]
100662146  CNTF; ciliary neurotrophic factor [KO:K05420]
100659658  CTF1; cardiotrophin-1 isoform X1 [KO:K05422]
100659942  cardiotrophin-2 [KO:K24382]
100671599  CLCF1; LOW QUALITY PROTEIN: cardiotrophin-like cytokine factor 1 [KO:K05421]
100664198  IL6R; interleukin-6 receptor subunit alpha [KO:K05055]
100669556  IL6ST; interleukin-6 receptor subunit beta isoform X2 [KO:K05060]
100655906  IL11RA; LOW QUALITY PROTEIN: interleukin-11 receptor subunit alpha [KO:K05056]
100661365  IL13RA1; interleukin-13 receptor subunit alpha-1 isoform X1 [KO:K05076]
100663910  IL13RA2; interleukin-13 receptor subunit alpha-2 [KO:K05077]
100675861  IL27RA; interleukin-27 receptor subunit alpha [KO:K19598]
100654399  IL31RA; interleukin-31 receptor subunit alpha [KO:K22630]
100666724  OSMR; oncostatin-M-specific receptor subunit beta [KO:K05057]
100658560  LIFR; LOW QUALITY PROTEIN: leukemia inhibitory factor receptor [KO:K05058]
100673654  CNTFR; ciliary neurotrophic factor receptor subunit alpha [KO:K05059]
100665398  IL10; interleukin-10 isoform X2 [KO:K05443]
100658487  IL19; interleukin-19 [KO:K05444]
100663567  interleukin-22-like [KO:K05445]
100664140  interleukin-22 [KO:K05445]
100664424  interleukin-22-like [KO:K05445]
100663852  interleukin-22-like [KO:K05445]
100658768  IL20; interleukin-20 isoform X1 [KO:K22667]
100659053  IL24; interleukin-24 [KO:K22668]
100668887  IL26; LOW QUALITY PROTEIN: interleukin-26 [KO:K05446]
100677387  IL10RA; interleukin-10 receptor subunit alpha [KO:K05134]
100667872  IL10RB; interleukin-10 receptor subunit beta isoform X2 [KO:K05135]
100666028  IL20RA; interleukin-20 receptor subunit alpha [KO:K05136]
100669996  LOW QUALITY PROTEIN: interleukin-20 receptor subunit alpha-like [KO:K05136]
100661481  IL20RB; interleukin-20 receptor subunit beta [KO:K05137]
100669119  IL22RA1; interleukin-22 receptor subunit alpha-1 [KO:K05138]
100665746  IL22RA2; interleukin-22 receptor subunit alpha-2 [KO:K05139]
100665137  IL12A; interleukin-12 subunit alpha [KO:K05406]
100657211  IL12B; interleukin-12 subunit beta [KO:K05425]
100656085  IL23A; interleukin-23 subunit alpha [KO:K05426]
100672726  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
100666176  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
100654129  IL23R; interleukin-23 receptor [KO:K05065]
100662962  somatotropin [KO:K05438]
100654812  PRL; prolactin [KO:K05439]
100663051  THPO; LOW QUALITY PROTEIN: thrombopoietin [KO:K06854]
100657655  CSF3; granulocyte colony-stimulating factor isoform X6 [KO:K05423]
100663871  LEP; leptin [KO:K05424]
100666267  EPOR; LOW QUALITY PROTEIN: erythropoietin receptor [KO:K05079]
100660760  GHR; growth hormone receptor [KO:K05080]
100664727  PRLR; prolactin receptor [KO:K05081]
100667327  MPL; LOW QUALITY PROTEIN: thrombopoietin receptor [KO:K05082]
100665706  CSF3R; LOW QUALITY PROTEIN: granulocyte colony-stimulating factor receptor [KO:K05061]
100665796  LEPR; leptin receptor isoform X1 [KO:K05062]
100665583  interferon alpha-5-like [KO:K05414]
100659984  interferon alpha-5-like [KO:K05414]
100660270  interferon alpha-5-like [KO:K05414]
100661986  interferon alpha-5-like [KO:K05414]
100662831  interferon alpha-5-like [KO:K05414]
100663685  interferon alpha-6-like [KO:K05414]
100660554  interferon alpha-5-like [KO:K05414]
100661135  interferon alpha-5-like [KO:K05414]
100666438  IFNB1; interferon beta [KO:K05415]
100659699  IFNE; interferon epsilon [KO:K05442]
100662737  IFNK; interferon kappa [KO:K05441]
100660429  uncharacterized protein LOC100660429 [KO:K22669]
100659865  interferon lambda-3-like [KO:K22669]
100660146  interferon lambda-3-like [KO:K22669]
100665300  interferon omega-1-like [KO:K05440]
100660848  interferon omega-2-like [KO:K05440]
100657514  interferon omega-1-like [KO:K05440]
100657422  interferon omega-2-like [KO:K05440]
100665867  interferon omega-2-like [KO:K05440]
100666154  interferon omega-2-like [KO:K05440]
100661419  LOW QUALITY PROTEIN: interferon omega-2-like [KO:K05440]
100667586  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
100672898  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
100669402  IFNLR1; interferon lambda receptor 1 isoform X1 [KO:K05140]
100663285  IFNG; interferon gamma [KO:K04687]
100665172  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100667304  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
100670137  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
100663544  PDGFB; platelet-derived growth factor subunit B isoform X2 [KO:K17386]
100659125  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100670735  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
100671240  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
100655548  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100676652  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
100665896  JAK3; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
100672245  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
100668424  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100656374  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
100669583  STAT3; signal transducer and activator of transcription 3 isoform X2 [KO:K04692]
100668145  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
100672448  signal transducer and activator of transcription 5A [KO:K11223]
100669299  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
100675819  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
100673235  IRF9; interferon regulatory factor 9 isoform X2 [KO:K04693]
100666357  CISH; cytokine-inducible SH2-containing protein isoform X1 [KO:K04701]
100664110  SOCS1; LOW QUALITY PROTEIN: suppressor of cytokine signaling 1 [KO:K04694]
100660067  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
100670741  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
100662743  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
100665538  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
100670207  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
100677654  SOCS7; suppressor of cytokine signaling 7 [KO:K04699]
100675268  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100676317  MCL1; induced myeloid leukemia cell differentiation protein Mcl-1 [KO:K02539]
100655646  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
100677514  PIM1; LOW QUALITY PROTEIN: serine/threonine-protein kinase pim-1 [KO:K04702] [EC:2.7.11.1]
100665874  MYC; myc proto-oncogene protein [KO:K04377]
100669703  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100668070  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100668683  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100671706  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100665288  aldehyde oxidase 4-like [KO:K00157] [EC:1.2.3.1]
100665571  AOX1; aldehyde oxidase 1 [KO:K00157] [EC:1.2.3.1]
100662726  aldehyde oxidase 3-like [KO:K00157] [EC:1.2.3.1]
100665003  LOW QUALITY PROTEIN: aldehyde oxidase 2-like [KO:K00157] [EC:1.2.3.1]
100660211  GFAP; glial fibrillary acidic protein isoform X2 [KO:K05640]
100671750  STAM; signal transducing adapter molecule 1 isoform X1 [KO:K04705]
100669167  STAM2; signal transducing adapter molecule 2 isoform X1 [KO:K04705]
100654678  PTPN2; tyrosine-protein phosphatase non-receptor type 2 isoform X2 [KO:K18026] [EC:3.1.3.48]
100676986  PTPN6; LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
100661096  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100663731  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100654250  PIAS1; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
100665384  PIAS2; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS2 [KO:K16063] [EC:2.3.2.-]
100667546  PIAS3; LOW QUALITY PROTEIN: E3 SUMO-protein ligase PIAS3 [KO:K16064] [EC:2.3.2.-]
100670291  PIAS4; E3 SUMO-protein ligase PIAS4 isoform X1 [KO:K16065] [EC:2.3.2.27]
100659575  FHL1; four and a half LIM domains protein 1 isoform X2 [KO:K14365]
100674758  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100655474  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100657379  SOS1; LOW QUALITY PROTEIN: son of sevenless homolog 1 [KO:K03099]
100656200  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100655727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100657948  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100658340  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100666266  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100653731  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100665045  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100675496  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100663184  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100657536  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100660187  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100660112  MTOR; LOW QUALITY PROTEIN: 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
lav04010  MAPK signaling pathway
lav04060  Cytokine-cytokine receptor interaction
lav04110  Cell cycle
lav04120  Ubiquitin mediated proteolysis
lav04151  PI3K-Akt signaling pathway
lav04210  Apoptosis
KO pathway
ko04630   
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