Protein kinase C isozymes differentially regulate promoters containing PEA-3/12-O-tetradecanoylphorbol-13-acetate response element motifs.
To investigate the regulation of promoters containing classical phorbol ester response sequences (PEA-3/12-O-tetradecanoylphorbol-13-acetate response element motifs) by protein kinase C (PKC) isozymes, co-transfections were performed in human dermal fibroblasts with a plasmid containing either the human collagenase promoter or the porcine urokinase plasminogen activator (uPA) promoter linked to the chloramphenicol acetyltransferase gene and a plasmid expressing an individual PKC isozyme. Using this experimental design, seven PKC isozymes were analyzed for their ability to trans-activate the collagenase and uPA promoters. Our results demonstrate that only PKC delta, epsilon, and eta trans-activated the collagenase promoter and that binding of Ap-1 family members to the collagenase 12-O-tetradecanoylphorbol-13-acetate response element (TRE) was not responsible for the isozyme-specific trans-activation. In contrast, the uPA promoter was stimulated by all of the PKC isozymes examined (PKC alpha, betaII, gamma, delta, epsilon, zeta, and eta). These results indicate that PKC isozymes differentially regulate promoters containing PEA-3/TRE motifs and suggest that individual isozymes play unique roles within the cell.
Reifel-Miller
A E
AE
Department of Diabetes Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
Conarty
D M
DM
Valasek
K M
KM
Iversen
P W
PW
Burns
D J
DJ
Birch
K A
KA
D001483:Base Sequence; D001769:Blood; D017364:Collagenases / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015533:Transcriptional Activation
D007527:Isoenzymes; D011493:Protein Kinase C; D017364:Collagenases; D013755:Tetradecanoylphorbol Acetate