Nat Med 2005,
PMID: 16041381
Jenkins, Brendan J; Grail, Dianne; Nheu, Thao; Najdovska, Meri; Wang, Bo; Waring, Paul; Inglese, Melissa; McLoughlin, Rachel M; Jones, Simon A; Topley, Nicholas; Baumann, Heinz; Judd, Louise M; Giraud, Andrew S; Boussioutas, Alex; Zhu, Hong-Jian; Ernst, Matthias
The latent transcription factor Stat3 is activated by gp130, the common receptor for the interleukin (IL)-6 cytokine family and other growth factor and cytokine receptors. Ligand-induced dimerization of gp130 leads to activation of the Stat1, Stat3 and Shp2-Ras-Erk signaling pathways. Here we assess genetically the contribution of exaggerated Stat3 activation to the phenotype of gp130 (Y757F/Y757F) mice, in which a knock-in mutation disrupts the negative feedback mechanism on gp130-dependent Stat signaling. Compared to gp130 (Y757F/Y757F) mice, reduced Stat3 activation in gp130 (Y757F/Y757F) Stat3(+/-) mice increased their lifespan, prevented splenomegaly, normalized exaggerated hepatic acute-phase response and lymphocyte trafficking, and suppressed the growth of spontaneously arising gastric adenomas in young mice. These lesions share histological features of gastric polyps in aging mice with monoallelic null mutations in Smad4, which encodes the common transducer for transforming growth factor (TGF)-beta signaling. Indeed, hyperactivation of Stat3 desensitizes gp130 (Y757F/Y757F) cells to the cytostatic effect of TGF-beta through transcriptional induction of inhibitory Smad7, thereby providing a novel link for cross-talk between Stat and Smad signaling in gastric homeostasis.
Diseases/Pathways annotated by Medline MESH: Adenoma, Stomach Neoplasms
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Text Mining Data
Stat3 → gp130: "
The latent transcription factor
Stat3 is
activated by
gp130 , the common receptor for the interleukin (IL)-6 cytokine family and other growth factor and cytokine receptors
"
Stat → gp130: "
Here we assess genetically the contribution of exaggerated Stat3 activation to the phenotype of gp130 ( Y757F/Y757F ) mice, in which a knock-in mutation disrupts the negative feedback mechanism on gp130 dependent Stat signaling
"
Manually curated Databases
No curated data.