The JAK (Janus kinase)-STAT (Signal Transducer and Activator of Transcription) signaling pathway plays an important role in transmitting information from extracellular polypeptide signals to target gene promoters in the nucleus. JAK-STAT signaling regulates many cellular processes including development, cell proliferation, differentiation, and apoptosis. The canonical JAK-STAT signaling pathway is activited by a cytokine binding to a cell-surface cytokine receptor. The intracellular domains of many cytokine receptors are physically associated with tyrosine kinases of the JAK family which are four mammalian JAKs (JAK1, 2, 3, Tyk2) that are associated with specific cytokine receptors. Activated JAKs can phosphorylate critical tyrosine residues on the receptor and their SH2 domains to recruit specific STATs leading to phosphorylation of the STAT. Growth factors,such as epidermal growth factor receptor or platelet-derived growth factor receptor, can stimulate STATs.
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