ANG II AT2 RECEPTORS INVOLVE PARTICIPATION OF THE COMPLEX SHP-1/c-Src/FAK AND ERK1/2 ACTIVATION.

SEGUIN LR.; BLANCO HM; CIUFFO GM.

Los Cocos, Cordoba, ARGENTINA

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine SISTAM 2010; 2010

While Ang II effects mediated by AT1 receptors are well-known, the signal transduction and functions of AT2 receptors remain unclear. The aim of this study was to elucidate the non-classical signaling pathway of Ang II AT2 receptors in PND15 rat hindbrain, a critical developmental stage. Membrane preparations were stimulated with Ang II in the presence or not of antagonists, the c-Src inhibitor PP2 or its inactive analog PP3. Following solubilization, proteins were immunoprecipitated with anti-AT2 or anti-SHP-1 antibodies. Ang II stimulation promotes SHP-1 association to AT2 receptors selectively. Immunocomplexes obtained with anti-AT2 or anti-SHP-1 exhibited PTPase activity, blocked by PD123319 (AT2 antagonist) or PP2. c-Src was present in these immunocomplexes and PP2 blocked SHP-1 tyr-phosphorylation as well as activation and SHP-1/c-Src association. AT2 immunocomplexes also contained FAK kinase but not paxillin. Besides, AT2 receptor´s activation induced activation of ERK1/2. Thus, Ang II AT2 receptors stimulation induced Tyr-phosphorylation of SHP-1 and immunocomplexes formation between AT2/SHP-1/c-Src/FAK. These results demonstrate an inducible signaling pathway of Ang II AT2 receptors suggesting a potential role in a critical stage of rat hindbrain development.