STATs, Signal Transducers and Activators of Transcription, are transcription factors that are phosphorylated by JAK kinases in response to cytokine activation to then dimerize and move into the nucleus to activate transcription of cytokine-responsive genes. There are at least 3 JAK kinases and at least six STATs, with different cytokines inducing different patterns of JAK and STAT activation. Cytokines that activate STAT3 include growth hormone, IL-6 family cytokines, and G-CSF. STAT3, as well as STAT5, induces progression through the cell cycle, prevents apoptosis and may be associated with cancer development in some cases. STAT3 plays an important role in normal development, particularly hematopoiesis. The importance of STAT3 is underscored by the failure of mice lacking STAT3 to survive embryogenesis. Crosstalk from pathways other than JAK kinases also leads to phosphorylation and activation of STAT3 as indicated by a role of mTOR (mammalian target of rapamycin, or p70 S6 kinase) and mitogen-activated protein kinase (MAP kinase) pathways in STAT3 activation and signaling.
Contributor: Cell Signaling Technology, Glenn Croston, PhD
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