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. |