COMPARATIVE STUDY OF ATYPICAL SIGNAL TRANSDUCTION OF AT2 RECEPTORS

MANZUR JIMENA; SEGUIN LEONARDO; CIUFFO GLADYS

Congreso; REUNIÓN DE LA SOCIEDAD DE BIOLOGÍA DE CUYO-XXX Annual Meeting; 2012

Studies of the signaling pathway of Ang II AT2 receptors appears controversial and cell-type specific. In the present study we compared the signaling pathways of Ang II AT2 receptors in two models: HeLa cells expressing AT2 receptors and membrane preparations from PND15 rat hindbrain. Previous studies in PND15 rat hindbrain evidenced the presence of FAK and SHP-1 in AT2 immunocomplexes following exposure to Ang II. Association of AT2-FAK-cSrc-RhoA was observed in HeLa-AT2 cells by immunoprecipation and western blot, maximal after 5 m in stimulation with Ang II (10-7M). FAK cleavage was observed in response to Ang II stimulation. In PND15 rat hindbrain preparations we observed phosphorylation of Tyr576/7 FAK but not Tyr397 FAK, induced by Ang II. Besides, ERK phosphorylation was induced by Ang II and blocked by Na3VO4 (PTPase inhibitor) or PP2, the c-Src inhibitor in hindbrain. In summary, two different models, a cell line over-expressing AT2 receptors and an ex vivo preparation, share a similar signaling pathway involving FAK, RhoA, c-Src and ERK in response to Ang II, an atypical transduction pathway for a GPCR family member.