cAMP signaling leads to activation and phosphorylation of Rap1b. Using cellular models where cAMP stimulates cell proliferation, we have demonstrated that cAMP-mediated activation, as well as phosphorylation of Rap1b, is critical for cAMP stimulation of DNA synthesis. To determine whether Rap1b stimulates mitogenesis in vivo, we have constructed a transgenic mouse where a constitutively active G12V-Rap1b, flanked by Cre recombinase LoxP sites, is followed by the dominant negative S17N mutant. Employing this novel mouse model, we have switched, in a tissue-specific (thyroid) and temporally controlled manner, the expression of Rap1b from a stimulatory to an inhibitory form. These experiments provide conclusive evidence that Rap1b is oncogenic in the thyroid in ways linked to transduction of the cAMP mitogenic signal.
cAMP-dependent Oncogenic Action of Rap1b in the Thyroid Gland*
F. Ribeiro-Neto,A. Leon,Julie Urbani-Brocard,L. Lou,A. Nyska,D. Altschuler
Published 2004 in Journal of Biological Chemistry
ABSTRACT
PUBLICATION RECORD
- Publication year
2004
- Venue
Journal of Biological Chemistry
- Publication date
2004-11-05
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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