Novel G Protein-Coupled Receptor Signalling Pathways in Cardiac Hypertrophy

摘要

In this presentation, we discuss two novel signaling pathways involving cardiac GPCR. Gq-coupled GPCR for catecholamines or angiotensin are very important in cardiovascular function and dysfunction. ERK5, a member of the MAPK family, has recently been shown to be involved in cardiac hypertrophy and to be stimulated by Galphaq-coupled GPCR via unknown mechanisms. We identify the atypical PKCxi as the functional link between these two key players in cardiovascular signaling and show that this novel Gaq/PKCxi axis is required for angiotensin-induce hypertrophy in mice. On the other hand, antibodies specific for the beta_1-adrenergic receptor (beta_1AR) are highly prevalent in patients with idiopathic dilated cardiomyopathy (DCM). We find that human beta_1AR - autoantibodies potently stimulate ERK1/2 in cardiac cells by using signalling pathways different from those triggered by classic beta-agonists. Our results suggest that these antibodies elicit a distinct beta_1AR active conformation leading to the engagement of signaling effectors different from those recruited by classic beta-agonists.