Journal of Biological Chemistry
Volume 282, Issue 3, 19 January 2007, Pages 1650-1657
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Mechanisms of Signal Transduction
RBCK1, a Protein Kinase CβI (PKCβI)-interacting Protein, Regulates PKCβ-dependent Function*

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RBCK1 (RBCC protein interacting with PKC 1) has originally been identified as a protein kinase CβI (PKCβI)-binding partner by a two-hybrid screen and as one of the gene transcripts that increases during adult cardiac hypertrophy. To address whether RBCK1 and PKCβI functions are interconnected, we used cultured neonatal myocytes where we previously found that the activity of PKCβI is required for an increase in cell size, also called hypertrophy. In this study, we showed that acute treatment of cardiac myocytes with phenylephrine, a prohypertrophic stimulant, transiently increased the association of RBCK1 with PKCβI within 1 min. A prolonged phenylephrine treatment also resulted in an increase of the interaction of the two proteins. Endogenous RBCK1 protein levels increased upon phenylephrine-induced hypertrophy. Further, adenovirus-based RBCK1 overexpression in the absence of phenylephrine increased cardiac cell size. This RBCK1-mediated hypertrophy required PKCβ activity, since the increase in cell size was inhibited when the RBCK1-expressing cells were treated with PKCβ-selective antagonists, supporting our previous observation that both PKCβI and PKCβII are required for hypertrophy. Unexpectedly, RBCK1-induced increased cell size was inhibited by phenylephrine. This effect correlated with a decrease in the level of both PKCβ isoforms. Most importantly, RNA interference for RBCK1 significantly inhibited the increase in cell size of cardiac myocytes following phenylephrine treatment. Our results suggest that RBCK1 binds PKCβI and is a key regulator of PKCβI function in cells and that, together with PKCβII, the three proteins are essential for developmental hypertrophy of cardiac myocytes.

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*

This project was supported by National Institutes of Health HL076675 (to D. M.-R.). D. M.-R. is the founder of KAI Pharmaceuticals, Inc., a company that plans to bring PKC regulators to the clinic. However, none of the work described here is based on or supported by the company. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement”in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1

Supported in part by postdoctoral awards from la Fondation pour la Recherche Médicale and from the American Heart Association.