KEGG PATHWAY: ko04630

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

Other DBs

GO:

0007259

Orthology

K00157

AOX; aldehyde oxidase [EC:1.2.3.1]

K00922

PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02161

BCL2; apoptosis regulator Bcl-2

K02539

MCL1; myeloid leukemia cell differntiation protein MCL-1

K02649

PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K02833

HRAS; GTPase HRas

K03099

SOS; son of sevenless

K04357

EGF; epidermal growth factor

K04359

PDGFA; platelet-derived growth factor subunit A

K04361

EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]

K04363

PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1]

K04364

GRB2; growth factor receptor-bound protein 2

K04366

RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04377

MYC; Myc proto-oncogene protein

K04447

JAK2; Janus kinase 2 [EC:2.7.10.2]

K04456

AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]

K04498

EP300, CREBBP, KAT3; E1A/CREB-binding protein [EC:2.3.1.48]

K04503

CCND1; G1/S-specific cyclin-D1

K04570

BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)

K04687

IFNG; interferon gamma

K04692

STAT3; signal transducer and activator of transcription 3

K04693

IRF9, ISGF3G, P48; interferon regulatory factor 9

K04694

SOCS1, JAB; suppressor of cytokine signaling 1

K04695

SOCS2, CIS2; suppressor of cytokine signaling 2

K04696

SOCS3, CIS3; suppressor of cytokine signaling 3

K04697

SOCS4; suppressor of cytokine signaling 4

K04698

SOCS5; suppressor of cytokine signaling 5

K04699

SOCS6_7; suppressor of cytokine signaling 6/7

K04701

CISH; cytokine inducible SH2-containing protein

K04702

PIM1; proto-oncogene serine/threonine-protein kinase Pim-1 [EC:2.7.11.1]

K04705

STAM; signal transducing adaptor molecule

K04706

PIAS1; E3 SUMO-protein ligase PIAS1 [EC:2.3.2.-]

K04736

IL3; interleukin 3

K04737

IL3RA, CD123; interleukin 3 receptor alpha

K04738

CSF2RB, IL3RB, CD131; cytokine receptor common subunit beta

K05055

IL6R, CD126; interleukin 6 receptor

K05056

IL11RA; interleukin 11 receptor alpha

K05057

OSMR; oncostatin M receptor

K05058

LIFR, CD118; leukemia inhibitory factor receptor

K05059

CNTFR; ciliary neurotrophic factor receptor

K05060

IL6ST, GP130, CD130; interleukin 6 signal transducer

K05061

CSF3R, CD114; granulocyte colony-stimulating factor receptor

K05062

LEPR, CD295; leptin receptor

K05063

IL12RB1, CD212; interleukin 12 receptor beta-1

K05064

IL12RB2; interleukin 12 receptor beta-2

K05065

IL23R; interleukin 23 receptor

K05066

CSF2RA, GMCSFR, CD116; granulocyte-macrophage colony-stimulating factor receptor alpha

K05067

IL5RA, CD125; interleukin 5 receptor alpha

K05068

IL2RA, CD25; interleukin 2 receptor alpha

K05069

IL2RB, CD122; interleukin 2 receptor beta

K05070

IL2RG, CD132; interleukin 2 receptor gamma

K05071

IL4R, CD124; interleukin 4 receptor

K05072

IL7R, CD127; interleukin 7 receptor

K05073

IL9R, CD129; interleukin 9 receptor

K05074

IL15RA, CD215; interleukin 15 receptor alpha

K05075

IL21R, CD360; interleukin 21 receptor

K05076

IL13RA1, CD213A1; interleukin 13 receptor alpha-1

K05077

IL13RA2, CD213A2; interleukin 13 receptor alpha-2

K05078

TSLPR; thymic stromal-derived lymphopoietin receptor

K05079

EPOR; erythropoietin receptor

K05080

GHR; growth hormone receptor

K05081

PRLR; prolactin receptor

K05082

TPOR, MPL, CD110; thrombopoietin receptor

K05089

PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1]

K05130

IFNAR1; interferon receptor 1

K05131

IFNAR2; interferon receptor 2

K05132

IFNGR1, CD119; interferon gamma receptor 1

K05133

IFNGR2; interferon gamma receptor 2

K05134

IL10RA, CD210A; interleukin 10 receptor alpha

K05135

IL10RB, CD210B; interleukin 10 receptor beta

K05136

IL20RA; interleukin 20 receptor alpha

K05137

IL20RB; interleukin 20 receptor beta

K05138

IL22RA1; interleukin 22 receptor alpha 1

K05139

IL22RA2; interleukin 22 receptor alpha 2

K05140

IFNLR1, IL28RA; interferon lambda receptor 1

K05405

IL6; interleukin 6

K05406

IL12A; interleukin 12A

K05414

IFNA; interferon alpha

K05415

IFNB; interferon beta

K05417

IL11; interleukin 11

K05418

OSM; oncostatin M

K05419

LIF; leukemia inhibitory factor

K05420

CNTF; ciliary neurotrophic factor

K05421

CLCF1, BSF3, CLC; cardiotrophin-like cytokine factor 1

K05422

CTF1, CT1; cardiotrophin 1

K05423

CSF3, GCSF; granulocyte colony-stimulating factor

K05424

LEP; leptin

K05425

IL12B; interleukin 12B

K05426

IL23A; interleukin 23 subunit alpha

K05427

CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor

K05428

IL5; interleukin 5

K05429

IL2; interleukin 2

K05430

IL4; interleukin 4

K05431

IL7; interleukin 7

K05432

IL9; interleukin 9

K05433

IL15; interleukin 15

K05434

IL21; interleukin 21

K05435

IL13; interleukin 13

K05436

TSLP; thymic stromal lymphopoietin

K05437

EPO; erythropoietin

K05438

GH; growth hormone

K05439

PRL; prolactin

K05440

IFNW; interferon omega

K05441

IFNK; interferon kappa

K05442

IFNE; interferon epsilon

K05443

IL10, CSIF; interleukin 10

K05444

IL19; interleukin 19

K05445

IL22, IL-TIF; interleukin 22

K05446

IL26; interleukin 26

K05447

IFNL1, IL29; interferon lambda 1

K05640

GFAP; glial fibrillary acidic protein

K05697

PTPN6, SHP1; tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48]

K06625

CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A

K06854

THPO; thrombopoietin

K07203

MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]

K07293

PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]

K10151

CCND2; G1/S-specific cyclin-D2

K10152

CCND3; G1/S-specific cyclin-D3

K11217

JAK1; Janus kinase 1 [EC:2.7.10.2]

K11218

JAK3; Janus kinase 3 [EC:2.7.10.2]

K11219

TYK2; non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]

K11220

STAT1; signal transducer and activator of transcription 1

K11221

STAT2; signal transducer and activator of transcription 2

K11222

STAT4; signal transducer and activator of transcription 4

K11223

STAT5A; signal transducer and activator of transcription 5A

K11224

STAT5B; signal transducer and activator of transcription 5B

K11225

STAT6; signal transducer and activator of transcription 6

K14365

FHL1, SLIM1; four and a half LIM domains protein 1

K16063

PIAS2; E3 SUMO-protein ligase PIAS2 [EC:2.3.2.-]

K16064

PIAS3; E3 SUMO-protein ligase PIAS3 [EC:2.3.2.-]

K16065

PIAS4; E3 SUMO-protein ligase PIAS4 [EC:2.3.2.27]

K16689

UPD; unpaired

K17386

PDGFB; platelet-derived growth factor subunit B

K18026

PTPN2, PTPT; tyrosine-protein phosphatase non-receptor type 2 [EC:3.1.3.48]

K19598

IL27RA; interleukin 27 receptor alpha

K19599

DOME; cytokine receptor domeless

K22629

IL27, IL27A; interleukin 27 subunit alpha

K22630

IL31RA; interleukin 31 receptor subunit alpha

K22631

IL31; interleukin 31

K22667

IL20; interleukin 20

K22668

IL24; interleukin 24

K22669

IFNL2_3, IL28; interferon lambda 2/3

K24382

CTF2; cardiotrophin 2

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