Transcript Slide 26 - Sigma

STAT3 Signaling Pathway
SIGMA-ALDRICH
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 kinase. 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.
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).