Entry
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
Ortholog table
Network
Element
N00053 Cytokine-Jak-STAT signaling pathway
N00094 EGF-Jak-STAT signaling pathway
N00415 IL10 family to Jak-STAT signaling pathway
N01554 IL2 family to Jak-STAT signaling pathway
N01555 Hormone-like-cytokine to Jak-STAT signaling pathway
N01556 IL6 family to Jak-STAT signaling pathway
N01557 IL12/23 to Jak-STAT signaling pathway
N01558 Type I interferon to Jak-STAT signaling pathway
N01559 Type II interferon to Jak-STAT signaling pathway
N01804 IL3 family to Jak-STAT signaling pathway
Drug
D00745 Interferon alfa-2a (USAN/INN)
D00746 Interferon beta-1b (USAN/INN)
D00747 Interferon gamma-1b (USAN/INN)
D02743 Celmoleukin (genetical recombination) (JP18)
D02744 Interferon alfacon-1 (USAN/INN)
D02745 Interferon alfa-2b (USAN)
D02747 Peginterferon alfa-2a (USAN/INN)
D02748 Peginterferon alfa-2b (USAN/INN)
D03231 Epoetin alfa (USAN/INN)
D03232 Epoetin beta (USAN/INN)
D03245 Nartograstim (genetical recombination) (JP18)
D03305 Interferon alfa (NAMALWA) (JP18)
D03357 Interferon gamma-1a (genetical recombination) (JAN)
D03651 Darbepoetin alfa (USAN/INN)
D03682 Denileukin diftitox (USAN/INN)
D03978 Eltrombopag olamine (JAN/USAN)
D04552 Interferon alfa-n1 (USAN)
D04553 Interferon alfa-n3 (USAN)
D04554 Interferon beta-1a (USAN)
D05066 Molgramostim (USAN/INN)
D05377 Pascolizumab (USAN/INN)
D05389 Pegnartograstim (USAN/INN)
D06556 Apilimod mesylate (USAN)
D06889 Pegfilgrastim (USAN/INN)
D08805 Interferon gamma-n1 (JAN)
D08844 Albinterferon alfa-2b (USAN)
D09024 Totrombopag choline (USAN)
D09633 Lebrikizumab (USAN/INN)
D09783 Tofacitinib citrate (JAN/USAN)
D09930 Mavrilimumab (USAN/INN)
D09946 Peginesatide (USAN/INN)
D09947 Peginesatide acetate (JAN/USAN)
D09960 Ruxolitinib phosphate (JAN/USAN)
D09979 Tralokinumab (USAN/INN)
D09998 Epoetin beta pegol (genetical recombination) (JAN)
D10015 Litgenprostucel-L (USAN)
D10078 Peginterferon lambda-1a (USAN)
D10306 Avatrombopag (USAN/INN)
D10307 Avatrombopag maleate (JAN/USAN)
D10308 Baricitinib (JAN/USAN/INN)
D10476 Lusutrombopag (JAN/USAN/INN)
D10483 Peginterferon beta-1a (USAN/INN)
D10717 Napabucasin (JAN/USAN/INN)
D10872 Filgotinib hydrochloride (USAN)
D10889 Momelotinib hydrochloride hydrate (JAN)
D10945 Itacitinib adipate (JAN/USAN)
D10994 Upadacitinib (USAN/INN)
D10995 Upadacitinib tartrate (USAN)
D11027 Ropeginterferon alfa-2b (INN)
D11046 Delgocitinib (JAN/USAN/INN)
D11048 Upadacitinib hydrate (JAN)
D11052 Risankizumab (USAN/INN)
D11079 Satralizumab (USAN/INN)
D11106 Filgotinib maleate (JAN/USAN)
D11188 Eflapegrastim (USAN/INN)
D11200 Pegilodecakin (USAN/INN)
D11296 Fedratinib hydrochloride (USAN)
D11538 Brepocitinib tosylate (USAN)
D11677 Gusacitinib hydrochloride (USAN)
D11817 Deucravacitinib (JAN/USAN)
D11821 Nogapendekin alfa (USAN/INN)
D11867 Deuruxolitinib phosphate (USAN)
D11953 Efmarodocokin alfa (USAN/INN)
D11962 Murizatoclax (USAN/INN)
D11970 Ritlecitinib tosylate (USAN)
D11986 Efbemalenograstim alfa (USAN/INN)
D12212 Ivarmacitinib sulfate (USAN)
D12308 Pivekimab sunirine (USAN)
D12328 Rezpegaldesleukin (USAN)
D12371 Nemvaleukin alfa (USAN/INN)
D12386 Melredableukin alfa (USAN/INN)
D12479 Lusvertikimab (USAN/INN)
D12502 Golidocitinib (USAN/INN)
D12575 Povorcitinib (USAN/INN)
D12576 Povorcitinib phosphate (USAN)
D12623 Nanrilkefusp alfa (USAN/INN)
D12625 Pegenzileukin (USAN/INN)
D12731 Anumigilimab (USAN/INN)
D12784 Casdozokitug (USAN/INN)
D12807 Ziltivekimab (USAN/INN)
D12888 Nogapendekin alfa inbakicept
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
3559 IL2RA; interleukin 2 receptor subunit alpha [KO:K05068 ]
3560 IL2RB; interleukin 2 receptor subunit beta [KO:K05069 ]
3561 IL2RG; interleukin 2 receptor subunit gamma [KO:K05070 ]
3601 IL15RA; interleukin 15 receptor subunit alpha [KO:K05074 ]
64109 CRLF2; cytokine receptor like factor 2 [KO:K05078 ]
1437 CSF2; colony stimulating factor 2 [KO:K05427 ]
3563 IL3RA; interleukin 3 receptor subunit alpha [KO:K04737 ]
3568 IL5RA; interleukin 5 receptor subunit alpha [KO:K05067 ]
1438 CSF2RA; colony stimulating factor 2 receptor subunit alpha [KO:K05066 ]
1439 CSF2RB; colony stimulating factor 2 receptor subunit beta [KO:K04738 ]
3976 LIF; LIF interleukin 6 family cytokine [KO:K05419 ]
1270 CNTF; ciliary neurotrophic factor [KO:K05420 ]
23529 CLCF1; cardiotrophin like cytokine factor 1 [KO:K05421 ]
3572 IL6ST; interleukin 6 cytokine family signal transducer [KO:K05060 ]
3590 IL11RA; interleukin 11 receptor subunit alpha [KO:K05056 ]
3597 IL13RA1; interleukin 13 receptor subunit alpha 1 [KO:K05076 ]
3598 IL13RA2; interleukin 13 receptor subunit alpha 2 [KO:K05077 ]
9466 IL27RA; interleukin 27 receptor subunit alpha [KO:K19598 ]
1271 CNTFR; ciliary neurotrophic factor receptor [KO:K05059 ]
3587 IL10RA; interleukin 10 receptor subunit alpha [KO:K05134 ]
3588 IL10RB; interleukin 10 receptor subunit beta [KO:K05135 ]
53832 IL20RA; interleukin 20 receptor subunit alpha [KO:K05136 ]
53833 IL20RB; interleukin 20 receptor subunit beta [KO:K05137 ]
58985 IL22RA1; interleukin 22 receptor subunit alpha 1 [KO:K05138 ]
116379 IL22RA2; interleukin 22 receptor subunit alpha 2 [KO:K05139 ]
3594 IL12RB1; interleukin 12 receptor subunit beta 1 [KO:K05063 ]
3595 IL12RB2; interleukin 12 receptor subunit beta 2 [KO:K05064 ]
1442 CSH1; chorionic somatomammotropin hormone 1 [KO:K05438 ]
1443 CSH2; chorionic somatomammotropin hormone 2 [KO:K05438 ]
1444 CSHL1; chorionic somatomammotropin hormone like 1 [KO:K05438 ]
1440 CSF3; colony stimulating factor 3 [KO:K05423 ]
4352 MPL; MPL proto-oncogene, thrombopoietin receptor [KO:K05082 ]
1441 CSF3R; colony stimulating factor 3 receptor [KO:K05061 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131 ]
3459 IFNGR1; interferon gamma receptor 1 [KO:K05132 ]
3460 IFNGR2; interferon gamma receptor 2 [KO:K05133 ]
5154 PDGFA; platelet derived growth factor subunit A [KO:K04359 ]
5155 PDGFB; platelet derived growth factor subunit B [KO:K17386 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
6774 STAT3; signal transducer and activator of transcription 3 [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 [KO:K11225 ]
1154 CISH; cytokine inducible SH2 containing protein [KO:K04701 ]
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 ]
9306 SOCS6; suppressor of cytokine signaling 6 [KO:K04699 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
4170 MCL1; MCL1 apoptosis regulator, BCL2 family member [KO:K02539 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
2670 GFAP; glial fibrillary acidic protein [KO:K05640 ]
10254 STAM2; signal transducing adaptor molecule 2 [KO:K04705 ]
8027 STAM; signal transducing adaptor molecule [KO:K04705 ]
8554 PIAS1; protein inhibitor of activated STAT 1 [KO:K04706 ] [EC:2.3.2.-]
9063 PIAS2; protein inhibitor of activated STAT 2 [KO:K16063 ] [EC:2.3.2.-]
10401 PIAS3; protein inhibitor of activated STAT 3 [KO:K16064 ] [EC:2.3.2.-]
2273 FHL1; four and a half LIM domains 1 [KO:K14365 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
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 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
Reference
Authors
Harrison DA
Title
The Jak/STAT pathway.
Journal
Reference
Authors
Kiu H, Nicholson SE
Title
Biology and significance of the JAK/STAT signalling pathways.
Journal
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
Reference
Authors
Fish EN, Platanias LC
Title
Interferon receptor signaling in malignancy: a network of cellular pathways defining biological outcomes.
Journal
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
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
Reference
Authors
Zoranovic T, Grmai L, Bach EA
Title
Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway.
Journal
Reference
Authors
Ungureanu D, Silvennoinen O
Title
SLIM trims STATs: ubiquitin E3 ligases provide insights for specificity in the regulation of cytokine signaling.
Journal
Reference
Authors
Richard AJ, Stephens JM
Title
The role of JAK-STAT signaling in adipose tissue function.
Journal
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
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
Reference
Authors
Rane SG, Reddy EP
Title
Janus kinases: components of multiple signaling pathways.
Journal
Reference
Authors
Heim MH
Title
The Jak-STAT pathway: specific signal transduction from the cell membrane to the nucleus.
Journal
Reference
Authors
Morris R, Kershaw NJ, Babon JJ
Title
The molecular details of cytokine signaling via the JAK/STAT pathway.
Journal
Reference
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
Reference
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
Related pathway
hsa04060 Cytokine-cytokine receptor interaction
KO pathway