KEGG PATHWAY: hsa04630

PATHWAY: hsa04630

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

Pathway map

hsa04630

Jak-STAT signaling pathway

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

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 (INN)
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)

Other DBs

BSID:

83077

GO:

0007259

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 (colony-stimulating factor, multiple) [KO:K04736]
1437	CSF2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
3567	IL5; interleukin 5 (colony-stimulating factor, eosinophil) [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 (interferon, beta 2) [KO:K05405]
3592	IL12A; interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) [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 (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) [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 (gp130, oncostatin M receptor) [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 myelocytomatosis viral oncogene homolog (avian) [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]
10251	SPRY3; sprouty homolog 3 (Drosophila) [KO:K04704]
10252	SPRY1; sprouty homolog 1, antagonist of FGF signaling (Drosophila) [KO:K04704]
10253	SPRY2; sprouty homolog 2 (Drosophila) [KO:K04704]
81848	SPRY4; sprouty homolog 4 (Drosophila) [KO:K04704]
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.-]
101060431	E3 SUMO-protein ligase PIAS3-like; K16064 E3 SUMO-protein ligase PIAS3 [EC:6.3.2.-] [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, E3 ubiquitin protein ligase C [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, E3 ubiquitin protein ligase B [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 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
5777	PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]

Reference

PMID:12039028

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

PMID:11994400

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

PMID:15003245

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

PMID:12479803

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

PMID:15032587

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

PMID:10409724

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

ko04630

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Ontology (1)   
   KEGG BRITE (1)   
Pathway (1)   
   BioSystems (1)   
Disease (9)   
   KEGG DISEASE (9)   
Drug (77)   
   KEGG DRUG (77)   
Genome (1)   
   KEGG GENOME (1)   
Gene (158)   
   KEGG GENES (158)   
All databases (247)   

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