Protein kinase C (PKC)ζ-mediated Gα <inf>q</inf> stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts

Carlota García-Hoz, Guzmán Sánchez-Fernández, Ramón García-Escudero, María Fernández-Velasco, Julia Palacios-García, Marisol Ruiz-Meana, Maria Teresa Díaz-Meco, Michael Leitges, Jorge Moscat, David García-Dorado, Lisardo Boscá, Federico Mayor, Catalina Ribas

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24 Citations (Scopus)

Abstract

Gq-coupled G protein-coupled receptors (GPCRs) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gα q-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gα q acts as an adaptor protein that facilitates PKCζ-mediated activation of ERK5 in epithelial cells. Because the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in cardiovascular Gq-dependent 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 Gq-coupled GPCRin neonatal and adult murine cardiomyocyte cultures and in cardiac fibroblasts. Stimulation of ERK5 by angiotensin II is blocked upon pharmacological inhibition or siRNA-mediated silencing of PKCζ in primary cultures of cardiac cells and in neonatal cardiomyocytes isolated from PKCζ-deficient mice. Moreover, upon chronic challenge with angiotensin II, these mice fail to promote the changes in the ERK5 pathway, in gene expression patterns, and in hypertrophic markers observed in wild-type animals. Taken together, our results show that PKCζ is essential for Gq-dependent ERK5 activation in cardiomyocytes and cardiac fibroblasts and indicate a key cardiac physiological role for the Gα q/PKCζ/ERK5 signaling axis. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)7792-7802
JournalJournal of Biological Chemistry
Volume287
Issue number10
DOIs
Publication statusPublished - 2 Mar 2012

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