Role of Jak kinases and STATs in cytokine signal transduction.
The Janus family tyrosine kinase-signal transducer and activator of transcription (Jak-STAT) signaling pathway is broadly used by interferons and type I cytokines. These cytokines and interferons activate Janus family tyrosine kinases (Jak kinases), which in turn phosphorylate and thereby activate STAT proteins. Before activation, STAT proteins are cytosolic proteins; after activation, however, they are translocated to the nucleus where they function as transcription factors. This review summarizes salient features of the Jak-STAT pathway and focuses on the functional role of the different Jak kinases and STATs in vivo.
Leonard
W J
WJ
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D019281:Dimerization; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000502:physiology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008894:Milk Proteins; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine / Q000502:physiology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D016207:Cytokines; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D007372:Interferons; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3