Classical, novel and atypical isoforms of PKC stimulate ANF- and TRE/AP-1-regulated-promoter activity 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
J B
JB
Department of Cardiac Medicine, National Heart and Lung Institute, University of London, UK.
Gillespie-Brown
J
J
Parker
P J
PJ
Sugden
P H
PH
Fuller
S J
SJ
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D002478:Cells, Cultured; D015870:Gene Expression; D006352:Heart Ventricles; D007527:Isoenzymes / Q000378:metabolism*; D008156:Luciferases / Q000096:biosynthesis; D016297:Mutagenesis, Site-Directed; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D017384:Sequence Deletion; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D007527:Isoenzymes; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D009320:Atrial Natriuretic Factor; D008156:Luciferases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate