Jak-STAT signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
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Jak-STAT signaling pathway - Homo sapiens (human) cluster_Cytokine Cytokine cluster_CytokineR CytokineR node1 1 node2 2 node4 15 Cas-Br-M (murine) ecotropic retroviral transforming sequence CBL Ubiquitin mediated proteolysis CBL->Ubiquitin mediated proteolysis +u signal transducing adaptor molecule (SH3 domain and ITAM motif) 1 STAM JAK STAM->JAK node5 6 STAT STAT->node5 STAT STAT dimers STAT->STAT dimers Homo/hetero STAT dimers PIAS PIAS->STAT SHP1 SHP1->JAK -p node18 6 SHP1->node18 -p node6 5 JAK->CBL JAK->STAT +p JAK->node6 JAK JAK->Ubiquitin mediated proteolysis +u SHP2 JAK->SHP2 +p PI3K JAK->PI3K +p P48 CBP SOCS IFNalpha->SOCS pim-1 oncogene PIM1 IFNalpha->PIM1 CIS IFNalpha->CIS SOCS->Ubiquitin mediated proteolysis Proliferation PIM1->Proliferation Growth PIM1->Growth Fate determination PIM1->Fate determination Development PIM1->Development Immunity PIM1->Immunity CIS->STAT STAT5 CIS->Proliferation CIS->Growth CIS->Fate determination CIS->Development CIS->Immunity node7 13 node8 c-Myc CycD node8->node7 c-Myc~CycD Cell cycle node8->Cell cycle BclXL Apoptosis BclXL->Apoptosis node13 Anti-apoptosis BclXL->node13 Spred node14 3 Spred->node14 Sprouty Sprouty->node14 GRB SHP2->GRB SOS GRB->SOS node9 2 SOS->node9 SOS SOS->node14 Ras/MAPK node10 12 PI3K->node10 PI3K AKT PI3K->AKT +p node11 29 AKT->node11 AKT AKT->Apoptosis AKT->node13 MAPK Signaling Pathway node12 2 MAPK Signaling Pathway->node12 node12->node8 node12->BclXL node12->Spred node12->Sprouty Lysosomal proteolysis node14->MAPK Signaling Pathway node15 4 node15->Lysosomal proteolysis node16 2 STAT dimers->IFNalpha node17 5 node17->CBL node17->Ubiquitin mediated proteolysis +u node18->node15 Endocytosis CytokineR 1 node18->CytokineR 1 CytokineR 2 node18->CytokineR 2 CytokineR 3 node18->CytokineR 3 CytokineR 1->node17 Link CytokineR 2->node16 CytokineR 2 CytokineR 2->node17 Link CytokineR 3->node17 Link node19 7 node19->node15 Endocytosis node19->node18 erythropoietin EPO EPO->node19 IFN IFN->node1 IFN IFN->node19 interleukin 10 IL10 IL10->node19 node3 IL2/3 node3->node2 IL2/3 node3->node19 interleukin 6 (interferon,beta 2) IL6 IL6->node4 IL6 IL6->node19 UPD print "