KEGG   PATHWAY: hsa04630Help
Entry
hsa04630                    Pathway                                

Name
Jak-STAT signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Jak-STAT signaling pathway
hsa04630

All organismsOrtholog table
Disease
H00408  
Type I diabetes mellitus
H00539  
PTEN hamartoma tumor syndrome (PHTS)
H00931  
Growth hormone insensitivity with immunodeficiency
H00935  
Cold-induced sweating syndrome (CISS) and Crisponi syndrome (CRISPS)
H01018  
Metachondromatosis
H01109  
Chronic mucocutaneous candidiasis (CMC)
H01122  
Pulmonary alveolar proteinosis (PAP)
H01217  
Primary localized cutaneous amyloidosis (PLCA)
H01227  
Inflammatory bowel disease
H01388  
Hyperprolactinemia
Drug
D00401  
Thiamazole (JP16/INN)
D00562  
Propylthiouracil (JP16/USP/INN)
D00745  
Interferon alfa-2a (genetical recombination) (JAN)
D00746  
Interferon beta-1b (genetical recombination) (JAN)
D00747  
Interferon gamma-1b (USAN/INN)
D00748  
Aldesleukin (USAN/INN)
D02596  
Tocilizumab (genetical recombination) (JAN)
D02691  
Somatropin (genetical recombination) (JAN)
D02743  
Celmoleukin (genetical recombination) (JP16)
D02744  
Interferon alfacon-1 (genetical recombination) (JAN)
D02745  
Interferon alfa-2b (genetical recombination) (JAN)
D02747  
Peginterferon alfa-2a (genetical recombination) (JAN)
D02748  
Peginterferon alfa-2b (generical recombination) (JAN)
D02749  
Teceleukin (genetical recombination) (JP16)
D03058  
Basiliximab (genetical recombination) (JAN)
D03231  
Epoetin alfa (genetical recombination) (JP16)
D03232  
Epoetin beta (genetical recombination) (JP16)
D03235  
Filgrastim (genetical recombination) (JP16)
D03245  
Nartograstim (genetical recombination) (JP16)
D03247  
Lenograstim (genetical recombination) (JP16)
D03304  
Interferon beta (JAN)
D03305  
Interferon alfa (BALL-1) (JAN)
D03357  
Interferon gamma-1a (genetical recombination) (JAN)
D03639  
Daclizumab (USAN/INN)
D03645  
Daniplestim (USAN/INN)
D03651  
Darbepoetin alfa (genetical recombination) (JAN)
D03682  
Denileukin diftitox (USAN/INN)
D03978  
Eltrombopag olamine (JAN/USAN)
D04032  
Epoetin delta (USAN)
D04552  
Interferon alfa-n1 (USAN)
D04554  
Interferon beta-1a (genetical recombination) (JAN)
D04695  
Leridistim (USAN/INN)
D04696  
Lestaurtinib (USAN/INN)
D04923  
Mepolizumab (USAN/INN)
D05036  
Milodistim (USAN/INN)
D05066  
Molgramostim (USAN/INN)
D05090  
Muplestim (genetical recombination) (JAN)
D05389  
Pegnartograstim (USAN/INN)
D05394  
Pegvisomant (genetical recombination) (JAN)
D05712  
Regramostim (USAN/INN)
D05803  
Sargramostim (USAN/INN)
D06556  
Apilimod mesylate (USAN)
D06889  
Pegfilgrastim (genetical recombination) (JAN)
D07231  
Methylthiouracil (INN)
D07519  
Benzylthiouracil
D08279  
Tozasertib (USAN)
D08344  
Tozasertib lactate (USAN)
D08805  
Interferon gamma-n1 (JAN)
D08844  
Albinterferon alfa-2b (USAN)
D08857  
Anrukinzumab (USAN)
D08985  
Reslizumab (USAN)
D08990  
Romiplostim (genetical recombination) (JAN)
D09024  
Totrombopag choline (USAN)
D09214  
Ustekinumab (genetical recombination) (JAN)
D09332  
Denenicokin (USAN/INN)
D09588  
Briakinumab (USAN/INN)
D09615  
Fezakinumab (USAN/INN)
D09633  
Lebrikizumab (USAN/INN)
D09662  
Rontalizumab (USAN/INN)
D09669  
Siltuximab (USAN/INN)
D09737  
Epoetin kappa (genetical recombination) (Epoetin alfa biosimilar 1) (JAN)
D09783  
Tofacitinib citrate (JAN/USAN)
D09874  
Benralizumab (USAN/INN)
D09897  
Enokizumab (USAN/INN)
D09930  
Mavrilimumab (USAN/INN)
D09946  
Peginesatide (USAN/INN)
D09947  
Peginesatide acetate (JAN/USAN)
D09959  
Ruxolitinib (USAN/INN)
D09960  
Ruxolitinib phosphate (JAN/USAN)
D09970  
Tofacitinib (USAN)
D09979  
Tralokinumab (USAN/INN)
D09998  
Epoetin beta pegol (genetical recombination) (JAN)
D10000  
Epoetin epsilon (genetical recombination) (JAN)
D10078  
Peginterferon lambda-1a (USAN)
D10080  
Sirukumab (USAN)
D10161  
Sarilumab (USAN)
D10242  
Lipegfilgrastim (USAN)
D10354  
Dupilumab (USAN)
D10365  
Gandotinib (USAN)
D10476  
Lusutrombopag (USAN/INN)
D10483  
Peginterferon beta-1a (USAN/INN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
7173  
TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
2056  
EPO; erythropoietin [KO:K05437]
2688  
GH1; growth hormone 1 [KO:K05438]
2689  
GH2; growth hormone 2 [KO:K05438]
1442  
CSH1; chorionic somatomammotropin hormone 1 (placental lactogen) [KO:K05438]
1443  
CSH2; chorionic somatomammotropin hormone 2 [KO:K05438]
5617  
PRL; prolactin [KO:K05439]
3458  
IFNG; interferon, gamma [KO:K04687]
3439  
IFNA1; interferon, alpha 1 [KO:K05414]
3440  
IFNA2; interferon, alpha 2 [KO:K05414]
3441  
IFNA4; interferon, alpha 4 [KO:K05414]
3442  
IFNA5; interferon, alpha 5 [KO:K05414]
3443  
IFNA6; interferon, alpha 6 [KO:K05414]
3444  
IFNA7; interferon, alpha 7 [KO:K05414]
3445  
IFNA8; interferon, alpha 8 [KO:K05414]
3446  
IFNA10; interferon, alpha 10 [KO:K05414]
3447  
IFNA13; interferon, alpha 13 [KO:K05414]
3448  
IFNA14; interferon, alpha 14 [KO:K05414]
3449  
IFNA16; interferon, alpha 16 [KO:K05414]
3451  
IFNA17; interferon, alpha 17 [KO:K05414]
3452  
IFNA21; interferon, alpha 21 [KO:K05414]
3456  
IFNB1; interferon, beta 1, fibroblast [KO:K05415]
3467  
IFNW1; interferon, omega 1 [KO:K05440]
56832  
IFNK; interferon, kappa [KO:K05441]
338376  
IFNE; interferon, epsilon [KO:K05442]
3586  
IL10; interleukin 10 [KO:K05443]
29949  
IL19; interleukin 19 [KO:K05444]
50604  
IL20; interleukin 20 [KO:K05444]
11009  
IL24; interleukin 24 [KO:K05444]
50616  
IL22; interleukin 22 [KO:K05445]
55801  
IL26; interleukin 26 [KO:K05446]
282616  
IFNL2; interferon, lambda 2 [KO:K05447]
282617  
IFNL3; interferon, lambda 3 [KO:K05447]
282618  
IFNL1; interferon, lambda 1 [KO:K05447]
3562  
IL3; interleukin 3 [KO:K04736]
1437  
CSF2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
3567  
IL5; interleukin 5 [KO:K05428]
3558  
IL2; interleukin 2 [KO:K05429]
3565  
IL4; interleukin 4 [KO:K05430]
3574  
IL7; interleukin 7 [KO:K05431]
3578  
IL9; interleukin 9 [KO:K05432]
3600  
IL15; interleukin 15 [KO:K05433]
59067  
IL21; interleukin 21 [KO:K05434]
3596  
IL13; interleukin 13 [KO:K05435]
85480  
TSLP; thymic stromal lymphopoietin [KO:K05436]
3569  
IL6; interleukin 6 [KO:K05405]
3592  
IL12A; interleukin 12A [KO:K05406]
3589  
IL11; interleukin 11 [KO:K05417]
5008  
OSM; oncostatin M [KO:K05418]
3976  
LIF; leukemia inhibitory factor [KO:K05419]
1270  
CNTF; ciliary neurotrophic factor [KO:K05420]
23529  
CLCF1; cardiotrophin-like cytokine factor 1 [KO:K05421]
1489  
CTF1; cardiotrophin 1 [KO:K05422]
1440  
CSF3; colony stimulating factor 3 (granulocyte) [KO:K05423]
3952  
LEP; leptin [KO:K05424]
3593  
IL12B; interleukin 12B [KO:K05425]
51561  
IL23A; interleukin 23, alpha subunit p19 [KO:K05426]
3563  
IL3RA; interleukin 3 receptor, alpha (low affinity) [KO:K04737]
1439  
CSF2RB; colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage) [KO:K04738]
3570  
IL6R; interleukin 6 receptor [KO:K05055]
3590  
IL11RA; interleukin 11 receptor, alpha [KO:K05056]
9180  
OSMR; oncostatin M receptor [KO:K05057]
3977  
LIFR; leukemia inhibitory factor receptor alpha [KO:K05058]
1271  
CNTFR; ciliary neurotrophic factor receptor [KO:K05059]
3572  
IL6ST; interleukin 6 signal transducer [KO:K05060]
1441  
CSF3R; colony stimulating factor 3 receptor (granulocyte) [KO:K05061]
3953  
LEPR; leptin receptor [KO:K05062]
3594  
IL12RB1; interleukin 12 receptor, beta 1 [KO:K05063]
3595  
IL12RB2; interleukin 12 receptor, beta 2 [KO:K05064]
149233  
IL23R; interleukin 23 receptor [KO:K05065]
1438  
CSF2RA; colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage) [KO:K05066]
3568  
IL5RA; interleukin 5 receptor, alpha [KO:K05067]
3559  
IL2RA; interleukin 2 receptor, alpha [KO:K05068]
3560  
IL2RB; interleukin 2 receptor, beta [KO:K05069]
3561  
IL2RG; interleukin 2 receptor, gamma [KO:K05070]
3566  
IL4R; interleukin 4 receptor [KO:K05071]
3575  
IL7R; interleukin 7 receptor [KO:K05072]
3581  
IL9R; interleukin 9 receptor [KO:K05073]
3601  
IL15RA; interleukin 15 receptor, alpha [KO:K05074]
50615  
IL21R; interleukin 21 receptor [KO:K05075]
3597  
IL13RA1; interleukin 13 receptor, alpha 1 [KO:K05076]
3598  
IL13RA2; interleukin 13 receptor, alpha 2 [KO:K05077]
64109  
CRLF2; cytokine receptor-like factor 2 [KO:K05078]
2057  
EPOR; erythropoietin receptor [KO:K05079]
2690  
GHR; growth hormone receptor [KO:K05080]
5618  
PRLR; prolactin receptor [KO:K05081]
4352  
MPL; myeloproliferative leukemia virus oncogene [KO:K05082]
3454  
IFNAR1; interferon (alpha, beta and omega) receptor 1 [KO:K05130]
3455  
IFNAR2; interferon (alpha, beta and omega) receptor 2 [KO:K05131]
3459  
IFNGR1; interferon gamma receptor 1 [KO:K05132]
3460  
IFNGR2; interferon gamma receptor 2 (interferon gamma transducer 1) [KO:K05133]
3587  
IL10RA; interleukin 10 receptor, alpha [KO:K05134]
3588  
IL10RB; interleukin 10 receptor, beta [KO:K05135]
53832  
IL20RA; interleukin 20 receptor, alpha [KO:K05136]
53833  
IL20RB; interleukin 20 receptor beta [KO:K05137]
58985  
IL22RA1; interleukin 22 receptor, alpha 1 [KO:K05138]
116379  
IL22RA2; interleukin 22 receptor, alpha 2 [KO:K05139]
163702  
IFNLR1; interferon, lambda receptor 1 [KO:K05140]
3716  
JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
3717  
JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
3718  
JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
7297  
TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
6772  
STAT1; signal transducer and activator of transcription 1, 91kDa [KO:K11220]
6773  
STAT2; signal transducer and activator of transcription 2, 113kDa [KO:K11221]
6774  
STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692]
6775  
STAT4; signal transducer and activator of transcription 4 [KO:K11222]
6776  
STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
6777  
STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
6778  
STAT6; signal transducer and activator of transcription 6, interleukin-4 induced [KO:K11225]
10379  
IRF9; interferon regulatory factor 9 [KO:K04693]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
8651  
SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
8835  
SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
9021  
SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
122809  
SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
9655  
SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
30837  
SOCS7; suppressor of cytokine signaling 7 [KO:K04699]
1154  
CISH; cytokine inducible SH2-containing protein [KO:K04701]
5292  
PIM1; pim-1 oncogene [KO:K04702] [EC:2.7.11.1]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
595  
CCND1; cyclin D1 [KO:K04503]
894  
CCND2; cyclin D2 [KO:K10151]
896  
CCND3; cyclin D3 [KO:K10152]
598  
BCL2L1; BCL2-like 1 [KO:K04570]
161742  
SPRED1; sprouty-related, EVH1 domain containing 1 [KO:K04703]
200734  
SPRED2; sprouty-related, EVH1 domain containing 2 [KO:K04703]
399473  
SPRED3; sprouty-related, EVH1 domain containing 3 [KO:K04703]
10252  
SPRY1; sprouty homolog 1, antagonist of FGF signaling (Drosophila) [KO:K04704]
10253  
SPRY2; sprouty homolog 2 (Drosophila) [KO:K17383]
81848  
SPRY4; sprouty homolog 4 (Drosophila) [KO:K17385]
10254  
STAM2; signal transducing adaptor molecule (SH3 domain and ITAM motif) 2 [KO:K04705]
8027  
STAM; signal transducing adaptor molecule (SH3 domain and ITAM motif) 1 [KO:K04705]
8554  
PIAS1; protein inhibitor of activated STAT, 1 [KO:K04706] [EC:6.3.2.-]
9063  
PIAS2; protein inhibitor of activated STAT, 2 [KO:K16063] [EC:6.3.2.-]
10401  
PIAS3; protein inhibitor of activated STAT, 3 [KO:K16064] [EC:6.3.2.-]
51588  
PIAS4; protein inhibitor of activated STAT, 4 [KO:K16065] [EC:6.3.2.-]
23624  
CBLC; Cbl proto-oncogene C, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
867  
CBL; Cbl proto-oncogene, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
868  
CBLB; Cbl proto-oncogene B, E3 ubiquitin protein ligase [KO:K04707] [EC:6.3.2.19]
5781  
PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
2885  
GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654  
SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655  
SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
5777  
PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
Reference
  Authors
Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW.
  Title
Signaling through the JAK/STAT pathway, recent advances and future challenges.
  Journal
Gene 285:1-24 (2002)
Reference
  Authors
Schindler CW.
  Title
Series introduction. JAK-STAT signaling in human disease.
  Journal
J Clin Invest 109:1133-7 (2002)
Reference
PMID:9716487
  Authors
Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L.
  Title
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway.
  Journal
Biochem J 334 ( Pt 2):297-314 (1998)
Reference
  Authors
Luo C, Laaja P.
  Title
Inhibitors of JAKs/STATs and the kinases: a possible new cluster of drugs.
  Journal
Drug Discov Today 9:268-75 (2004)
Reference
  Authors
Hou SX, Zheng Z, Chen X, Perrimon N.
  Title
The Jak/STAT pathway in model organisms: emerging roles in cell movement.
  Journal
Dev Cell 3:765-78 (2002)
Reference
  Authors
Alexander WS, Hilton DJ.
  Title
The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response.
  Journal
Annu Rev Immunol 22:503-29 (2004)
Reference
  Authors
Kim H, Baumann H.
  Title
Dual signaling role of the protein tyrosine phosphatase SHP-2 in regulating expression of acute-phase plasma proteins by interleukin-6 cytokine receptors in hepatic cells.
  Journal
Mol Cell Biol 19:5326-38 (1999)
KO pathway
 

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