Jaks and Stats in signaling by the cytokine receptor superfamily.
Many cytokines mediate their biological effects through interaction with a distinct family of receptors termed the cytokine receptor superfamily. Although members of this family lack catalytic domains, they couple ligand binding to tyrosine phosphorylation. Recent studies have shown that a novel family of cytoplasmic protein tyrosine kinases, termed the Janus kinases (Jaks), associate with the cytokine receptors and are catalytically activated after ligand binding. The activated Jaks phosphorylate and activate members of a novel family of transcription factors termed signal transducers and activators of transcription (Stats). In addition, many cytokines induce the phosphorylation of SHC, Vav and the p85 subunit of PI-3 kinase. The region of the receptors proximal to the cytoplasmic membrane is required for Jak association, mitogenesis, Stat activation and Vav phosphorylation. The membrane-distal region, which contains the major sites of tyrosine phosphorylation, is required for phosphorylation of SHC and p85, not for mitogenesis, thus allowing functional dissection of the signaling pathways activated by cytokines.
Ihle
J N
JN
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105.
Kerr
I M
IM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053612:Janus Kinases; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine / Q000502:physiology*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors
D016207:Cytokines; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; 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; D053612:Janus Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C085845:hop protein, Drosophila