PKC Ζ-Mediated G Α Q Stimulation of the Erk 5 Pathway in Cardiomyocytes and Cardiac Fibroblasts (original) (raw)

2011

Abstract

Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gαqmediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gαq acts as an adaptor protein that facilitates PKCζmediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in cardiovascular Gqdependent signaling using both cultured cardiac cell types and chronic administration of angiotensin II in mice. We find that PKCζ is required for the activation of the ERK5 pathway by Gqcoupled GPCR in neonatal and adult murine cardiomyocyte cultures and in cardiac fibroblasts. Stimulation of ERK5 by angiotensin II is blocked upon pharmacological inhibition or siRNAmediated silencing of PKCζ in primary cultures of cardiac cells and in neonatal ...

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