| First Author | García-Hoz C | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 10 | Pages | 7792-802 |
| PubMed ID | 22232556 | Mgi Jnum | J:182771 |
| Mgi Id | MGI:5316561 | Doi | 10.1074/jbc.M111.282210 |
| Citation | Garcia-Hoz C, et al. (2012) Protein kinase C (PKC)zeta-mediated Galphaq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts. J Biol Chem 287(10):7792-802 |
| abstractText | Gq-coupled G protein-coupled receptors (GPCRs) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Galpha(q)-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Galpha(q) acts as an adaptor protein that facilitates PKCzeta-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 PKCzeta is required for the activation of the ERK5 pathway by Gq-coupled GPCR in 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 PKCzeta in primary cultures of cardiac cells and in neonatal cardiomyocytes isolated from PKCzeta-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 PKCzeta is essential for Gq-dependent ERK5 activation in cardiomyocytes and cardiac fibroblasts and indicate a key cardiac physiological role for the Galpha(q)/PKCzeta/ERK5 signaling axis. |
