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Publication : cAMP-dependent oncogenic action of Rap1b in the thyroid gland.

First Author  Ribeiro-Neto F Year  2004
Journal  J Biol Chem Volume  279
Issue  45 Pages  46868-75
PubMed ID  15331589 Mgi Jnum  J:94485
Mgi Id  MGI:3512864 Doi  10.1074/jbc.M406858200
Citation  Ribeiro-Neto F, et al. (2004) cAMP-dependent oncogenic action of Rap1b in the thyroid gland. J Biol Chem 279(45):46868-75
abstractText  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.
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