STAT3 Signaling Pathway

STAT3 Signaling Pathway

Signal Transducers and Activators of Transcription (STATs) are transcription factors that are phosphorylated by JAK kinases in response to cytokine activation of a cell surface receptor tyrosine kinases. Upon activation, the STATs dimerize and are localized to the nucleus where they activate transcription of cytokine-responsive genes. There are at least three JAK kinases and at least six STAT proteins involved in this complex signaling pathway. 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 upregulates oncogenes, such as c-myc and bcl-X and may play a role in oncogenesis. STAT3 has been shown to play a critical role in 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 MAP kinase pathways in STAT3 activation and signaling.

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References:

Ihle, J.N., The STAT family in cytokine signaling. Curr. Opin. Cell Biol., 13, 211-217 (2001).

Bowman T., et al., STATs in oncogenesis. Oncogene, 19, 2474-2488 (2000). Turkson J, Jove R., STAT proteins: novel molecular targets for cancer drug discovery. Oncogene, 19, 6613-6626 (2000).

Bromberg J.F., et al., STAT3 as an oncogene. Cell, 98, 295-303 (1999).