G-protein coupled receptors (GPCRs) are integral membrane proteins characterized as having seven transmembrane alpha-helices. These receptors are important targets for biomedical studies, and approximately 40% of the currently marketed drugs act on them. The angiotensin II type 1 (AT1) receptor is a GPCR, and the main receptor of the renin-angiotensin system (SRA), mediating important pathophysiological effects in different tissues and organs, and being the target of the system's main effector molecule angiotensin II (AngII). Considering the pharmacological importance of the AT1 receptor, several studies have focused on the search for selective agonists that induce the activation of a particular signaling pathway in detriment of others, as well as on understanding their roles in cell signaling. This project proposes an innovative approach to study this phenomenon, which is by proteomic analysis. Cells expressing the AT1 receptor will be stimulated with different ligands including the ones previously described as selective. Our aims are to better understand what type of cellular responses these ligands generate, which proteins are activated, and in which cellular compartment(s) the activated proteins are located. The study shows promise for identifying new drug targets and for better understanding the mechanisms involved in the selective agonism. For the project development, we will count with the active participation of Professor Vitor M. Faça, a collaborator in our Thematic Project with vast experience in proteomic analyses.
News published in Agência FAPESP Newsletter about the scholarship: