KEGG   PATHWAY: ko04630
Entry
ko04630                     Pathway                                

Name
JAK-STAT signaling pathway
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
ko04630  JAK-STAT signaling pathway
ko04630

Disease
H00286  Crohn disease
H00408  Type 1 diabetes mellitus
H00931  Growth hormone insensitivity with immunodeficiency
H00935  Cold-induced sweating syndrome
H01018  Metachondromatosis
H01109  Chronic mucocutaneous candidiasis
H01122  Congenital pulmonary alveolar proteinosis
H01217  Primary localized cutaneous amyloidosis
H01227  Inflammatory bowel disease (IBD)
H01388  Hyperprolactinemia
H01466  Ulcerative colitis
H01479  Castleman disease
H01502  Sjogren syndrome
H01605  Myelofibrosis
H01672  Juvenile idiopathic arthritis
H02037  Laron syndrome
H02039  Kowarski syndrome
H02059  Leptin deficiency
H02060  Leptin receptor deficiency
H02254  Craniosynostosis and dental anomalies
Other DBs
GO: 0007259
Orthology
K05429  interleukin 2
K04736  interleukin 3
K05430  interleukin 4
K05428  interleukin 5
K05405  interleukin 6
K05431  interleukin 7
K05432  interleukin 9
K05443  interleukin 10
K05417  interleukin 11
K05406  interleukin 12A
K05425  interleukin 12B
K05435  interleukin 13
K05433  interleukin 15
K05492  interleukin 17D
K05444  interleukin 19
K22667  interleukin 20
K05434  interleukin 21
K05445  interleukin 22
K05426  interleukin 23 subunit alpha
K22668  interleukin 24
K05414  interferon alpha
K05415  interferon beta
K04687  interferon gamma
K05442  interferon epsilon
K05441  interferon kappa
K05447  interferon lambda 1
K22669  interferon lambda 2/3
K05440  interferon omega
K05418  oncostatin M
K05419  leukemia inhibitory factor
K05436  thymic stromal lymphopoietin
K05422  cardiotrophin 1
K24382  cardiotrophin 2
K05427  granulocyte-macrophage colony-stimulating factor
K16689  unpaired
K05420  ciliary neurotrophic factor
K05423  granulocyte colony-stimulating factor
K05437  erythropoietin
K05438  growth hormone
K05424  leptin
K06854  thrombopoietin
K05439  prolactin
K04357  epidermal growth factor
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05068  interleukin 2 receptor alpha
K05069  interleukin 2 receptor beta
K05070  interleukin 2 receptor gamma
K04737  interleukin 3 receptor alpha
K05071  interleukin 4 receptor
K05067  interleukin 5 receptor alpha
K05055  interleukin 6 receptor
K05072  interleukin 7 receptor
K05073  interleukin 9 receptor
K05134  interleukin 10 receptor alpha
K05135  interleukin 10 receptor beta
K05056  interleukin 11 receptor alpha
K05063  interleukin 12 receptor beta-1
K05064  interleukin 12 receptor beta-2
K05076  interleukin 13 receptor alpha-1
K05077  interleukin 13 receptor alpha-2
K05074  interleukin 15 receptor alpha
K05136  interleukin 20 receptor alpha
K05137  interleukin 20 receptor beta
K05075  interleukin 21 receptor
K05138  interleukin 22 receptor alpha 1
K05139  interleukin 22 receptor alpha 2
K05065  interleukin 23 receptor
K19598  interleukin 27 receptor alpha
K05060  interleukin 6 signal transducer
K05130  interferon receptor 1
K05131  interferon receptor 2
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K05140  interferon lambda receptor 1
K05057  oncostatin M receptor
K05058  leukemia inhibitory factor receptor
K05078  thymic stromal-derived lymphopoietin receptor
K05059  ciliary neurotrophic factor receptor
K05066  granulocyte-macrophage colony-stimulating factor receptor alpha
K04738  cytokine receptor common subunit beta
K05061  granulocyte colony-stimulating factor receptor
K05079  erythropoietin receptor
K05080  growth hormone receptor
K05062  leptin receptor
K05082  thrombopoietin receptor
K05081  prolactin receptor
K19599  cytokine receptor domeless
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K04363  platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  platelet-derived growth factor receptor beta [EC:2.7.10.1]
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11218  Janus kinase 3 [EC:2.7.10.2]
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]
K11220  signal transducer and activator of transcription 1
K11221  signal transducer and activator of transcription 2
K04692  signal transducer and activator of transcription 3
K11222  signal transducer and activator of transcription 4
K11223  signal transducer and activator of transcription 5A
K11224  signal transducer and activator of transcription 5B
K11225  signal transducer and activator of transcription 6
K04701  cytokine inducible SH2-containing protein
K04694  suppressor of cytokine signaling 1
K04695  suppressor of cytokine signaling 2
K04696  suppressor of cytokine signaling 3
K04697  suppressor of cytokine signaling 4
K04698  suppressor of cytokine signaling 5
K04699  suppressor of cytokine signaling 6/7
K02161  apoptosis regulator Bcl-2
K02539  myeloid leukemia cell differntiation protein MCL-1
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04702  proto-oncogene serine/threonine-protein kinase Pim-1 [EC:2.7.11.1]
K04377  Myc proto-oncogene protein
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K06625  cyclin-dependent kinase inhibitor 1A
K00157  aldehyde oxidase [EC:1.2.3.1]
K05640  glial fibrillary acidic protein
K04705  signal transducing adaptor molecule
K18026  tyrosine-protein phosphatase non-receptor type 2 [EC:3.1.3.48]
K05697  tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48]
K04693  interferon regulatory factor 9
K04498  E1A/CREB-binding protein [EC:2.3.1.48]
K04706  E3 SUMO-protein ligase PIAS1 [EC:2.3.2.-]
K16063  E3 SUMO-protein ligase PIAS2 [EC:2.3.2.-]
K16064  E3 SUMO-protein ligase PIAS3 [EC:2.3.2.-]
K16065  E3 SUMO-protein ligase PIAS4 [EC:2.3.2.27]
K14365  four and a half LIM domains protein 1
K07293  tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]
K04364  growth factor receptor-bound protein 2
K03099  son of sevenless
K02833  GTPase HRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K07203  serine/threonine-protein kinase mTOR [EC:2.7.11.1]
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
Related
pathway
ko04010  MAPK signaling pathway
ko04060  Cytokine-cytokine receptor interaction
ko04110  Cell cycle
ko04120  Ubiquitin mediated proteolysis
ko04151  PI3K-Akt signaling pathway
ko04210  Apoptosis
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