STAT3 Signaling Pathway

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STAT3 Signaling Pathway
SIGMA-ALDRICH
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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).