Cytokine signaling through the JAK/STAT pathway

Cytokine signaling through the JAK/STAT pathway. Cytokines, including IFNs -α, -β and -γ, IL-6 and LIF, signal through receptor complexes (see inset) that activate the JAK/STAT pathway. Activation of STAT transcription factors, particularly STAT1 and STAT3, induces SOCS1 and SOCS3 gene expression. Both SOCS1 and SOCS3 inhibit JAK activity through their KIR. However, SOCS1 binds primarily to phosphorylated, receptor-associated JAK proteins through its SH2 domain, whereas the SH2 domain of SOCS3 binds to phosphorylated tyrosine residues in the cytoplasmic domain of receptors. In some cases, however, SOCS1 can bind to phosphorylated receptors and SOCS3 can interact directly with JAKs. All of these interactions terminate STAT activation and suppress downstream gene expression.

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SOCS1 and SOCS3 in the control of CNS immunity. () Brandi J. Baker, et al. Trends Immunol. ;30(8):392-400. Figure: F2. All organisms Rattus norvegicus Homo sapiens Mus musculus Danio rerio

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