Regulation of CYP11B2 gene expression by protein kinase C.

Bisindolylmaleimide, a protein kinase C (PKC) inhibitor, was shown to stimulate the hamster CYP11B2 promoter activity in transfected NCI-H295 cells. In this study we have found that TPA, an activator of PKC, also inhibited the hamster CYP11B2 promoter activity. DAG-dependent PKC alpha and PKC epsilon, and atypical PKC zeta were detected in hamster adrenal zona glomerulosa, whereas the isoforms alpha, epsilon, zeta and theta were found in NCI-H295 cells. CYP11B2 promoter activity was inhibited in cells co-transfected with constitutively active PKC alpha and epsilon mutants, whereas it was increased with the constitutively active PKC zeta mutant. Dominant negative PKC alpha, epsilon and zeta mutants stimulated the promoter activity. Gö6976, a specific inhibitor of classical PKCs, enhanced promoter activity, providing further evidence that PKC alpha, the only classical PKC revealed in hamster adrenal and NCI-H295 cells, was involved in the promoter inhibition.