All subfamilies of PKC (classical, novel, and atypical) can stimulate ANF-promoter activity, suggesting they may contribute to the hypertrophic response in ventricular cardiomyocytes.
Cultured neonatal rat ventricular myocytes were co-transfected with expression plasmids encoding protein kinase C (PKC) isoforms from each of the PKC subfamilies (classical PKC-alpha, novel PKC-epsilon or atypical PKC-zeta) together with an atrial natriuretic factor (ANF) reporter plasmid. Each PKC had been rendered constitutively active by a single Ala-->Glu mutation or a small deletion in the inhibitory pseudosubstrate site. cPKC-alpha, nPKC-epsilon or aPKC-zeta expression plasmids each stimulated ANF-promoter activity and expression of a reporter gene under the control of a 12-O-tetradecanoylphorbol 13-acetate-response element (TRE). Upregulation of the ANF promoter is characteristic of the hypertrophic response in the heart ventricle and a TRE is present in the ANF promoter. Thus all subfamilies of PKC may have the potential to contribute to hypertrophic response in cardiomyocytes.
Decock et al. (1994) studied this question.