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J. Biol. Chem., Vol. 276, Issue 11, 8021-8028, March 16, 2001
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From the Department of Biochemistry, Faculty of Medicine,
University of Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
We reported previously that the protein
kinase C (PKC) inhibitor GF109203X stimulated the hamster
CYP11B2 promoter activity in transfected NCI-H295 cells.
PKC
Control of CYP11B2 Gene Expression through
Differential Regulation of Its Promoter by Atypical and Conventional
Protein Kinase C Isoforms*
,
, -
, and -
were detected in hamster adrenal zona
glomerulosa and NCI-H295 cells, and PKC
in NCI-H295 cells.
12-O-Tetradecanoylphorbol-13-acetate (TPA) inhibited basal
and stimulated cytochrome P450 aldosterone synthase mRNA expression
by angiotensin (AII), dibutyryl cyclic adenosine 3':5'-monophosphate
(Bt2cAMP), or KCl in NCI-H295 cells. Basal CYP11B2 promoter activity was inhibited in cells
cotransfected with constitutively active (CA) PKC, -, and -
mutants, whereas it was increased with CA-PKC. Dominant negative
(DN) PKC, -, -, and - mutants stimulated the promoter
activity. AII-, KCl-, and Bt2cAMP-stimulatory effects were
abolished in cells cotransfected with CA-PKC, -, or -. The
effect of Bt2cAMP was abolished by CA-PKC but AII and
KCl were still able to enhance the promoter activity. DN-PKC, -,
-, or - did not inhibit these effects. Gö6976 enhanced
promoter activity, providing further evidence that PKC was involved.
Various CYP11B2 promoter constructs were used to identify
the area associated with TPA and PKC inhibition. TPA and CA-PKC,
-, or - abolished the effects of AII, KCl, and
Bt2cAMP on the activity of 
102 and longer constructs. In summary, our findings suggest that the hamster CYP11B2 gene
is under differential control by conventional () and atypical
() PKC.
*
This work was supported in part by Medical Research Council
of Canada Grant MT-10983 (to J.-G. L.) and a grant from the
Heart and Stroke Foundation of Canada (to J.-G. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Chercheur Boursier de Carrière from the Fonds de la
Recherche en Santé du Québec. To whom correspondence should
be addressed.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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