Regulation of CYP11B2 Gene Expression by Protein Kinase C

Abstract

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 α and PKC ω, and atypical PKC were detected in hamster adrenal zona glomerulosa, whereas the isoforms α, β were found in NCI-H295 cells. CYP11B2 promoter activity was inhibited in cells co-transfected with constitutively active PKC α and mutants, whereas it was increased with the constitutively active PKC mutant. Dominant negative PKC α, mutants stimulated the promoter activity. Gö6976, a specific inhibitor of classical PKCs, enhanced promoter activity, providing further evidence that PKC α, the only classical PKC revealed in hamster adrenal and NCI-H295 cells, was involved in the promoter inhibition.