Stat3 is a key signaling molecule for many cytokines and growth-factor receptors and is required for murine fetal development. Additionally, Stat3 is constitutively activated in a number of human tumors and possesses oncogenic potential and anti-apoptotic activities. Stat3 is activated by tyrosine phosphorylation at Tyr705, which induces dimerization, nuclear translocation and DNA binding. Transcriptional activation seems to be regulated by serine phosphorylation at Ser727, apparently via the MAPK or mTOR pathways. Stat3 isoform expression appears to reflect biological function: the relative expression levels of Stat3alpha (86kD) and Stat3beta (79kD) depend on cell type, ligand exposure or maturation stage of the cells. It is notable that Stat3beta lacks the serine phosphorylation site within the C-terminal transcriptional activation domain.
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