RBCK1, a protein kinase CbetaI (PKCbetaI)-interacting protein, regulates PKCbeta-dependent function.

RBCK1 (RBCC protein interacting with 1) has originally been identified as a protein kinase CbetaI partner by a two-hybrid screen and as one of the gene transcripts that increases during adult cardiac hypertrophy. To address whether RBCK1 and functions are interconnected, we used cultured neonatal myocytes where we previously found that the activity of duanyu1531betaI 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 duanyu1531betaI 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 activity, since the increase in cell size was inhibited when the RBCK1-expressing cells were treated with antagonists, supporting our previous observation that both duanyu1531betaI and 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 duanyu1531beta 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 duanyu1531betaI and is a key regulator of duanyu1531betaI function in cells and that, together with the three proteins are essential for developmental hypertrophy of cardiac myocytes.

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