A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function

Protein kinase C (PKC) isozymes translocate to unique subcellular sites following activation. We previously suggested that translocation of activated isozymes is required for their function and that in addition to binding to lipids, translocation involves binding of the activated isozymes to specific anchoring proteins (receptors for activated protein kinase C. Using cultured cardiomyocytes we identified inhibitors, the V1 fragment of epsilon PKC (epsilon V1), and an 8-amino acid peptide derived from it that selectively inhibited the translocation of epsilon PKC. Inhibition of epsilon PKC translocation but not inhibition of delta or beta PKC translocation specifically blocked phorbol ester- or norepinephrine-mediated regulation of contraction. These isozyme-selective translocation inhibitors provide novel tools to determine the function of individual PKC isozymes in intact cells.