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 phorbo l ester response sequences (PEA-3/12-O-tetradecanoylphorbol-13-acetate response element motifs) by protein kinase C (PRC) isozymes, co-trans fections were performed in human dermal fibroblasts with a plasmid con taining either the human collagenase promoter or the porcine urokinase plasminogen activator (uPA) promoter linked to the chloramphenicol ac etyl-transferase gene and a plasmid expressing an individual PRC isozy me. Using this experimental design, seven PKC isozymes were analyzed f or their ability to transactivate the collagenase and uPA promoters. O ur results demonstrate that only PKC delta, epsilon, and eta trans-act ivated the collagenase promoter and that binding of Ap-l family member s to the collagenase 12-O-tetradecanoylphorbol-13-acetate response ele ment (TRE) was not responsible for the isozyme-specific trans-activati on. in contrast, the uPA promoter was stimulated by all of the PKC iso zymes examined (PKC alpha, beta II, gamma, delta, 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.