Regulation of CYP11B2 gene expression by protein kinase C.

Bisindolylmaleimide, a protein kinase C (PKC) inhibitor, was shown to stimu late the hamster CYP11B2 promoter activity in transfected NCI-H295 cells. I n this study we have found that TPA, an activator of PKC, also inhibited th e hamster CYP11B2 promoter activity. DAG-dependent PKC alpha and PKC epsilo n, 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 wit h constitutively active PKC alpha and epsilon mutants, whereas it was incre ased with the constitutively active PKC zeta mutant. Dominant negative PKC alpha, epsilon and zeta mutants stimulated the promoter activity. Go6976, a specific inhibitor of classical PKCs, enhanced promoter activity, providin g further evidence that PKC alpha, the only classical PKC revealed in hamst er adrenal and NCI-H295 cells, was involved in the promoter inhibition.