Stimulus-dependent subcellular localization of activated protein kinase C; a study with acidic fibroblast growth factor and transforming growth factor-beta 1 in cardiac myocytes.
Protein kinase C (PKC) isozymes regulate a number of cardiac functions including contractility, gene expression, and hypertrophy. There are at least six PKC isozymes in neonatal rat ventricular myocytes. We have shown previously that stimulation of cardiac myocytes in culture with norepinephrine (NE) or phorbol 12-myristate 13-acetate (PMA) results in translocation of each isozyme to distinct subcellular sites. In the present work, we demonstrated that PKC isozymes vary in their sensitivity to stimulation by acidic fibroblast growth factor (aFGF) and transforming growth factor-beta 1 (TGF-beta 1). Moreover, immunocytochemical studies indicated differences in the subcellular localization of activated isozymes following stimulation with each growth factor. These data suggest that the site of translocation and the resulting function of individual PKC isozymes are distinct for different PKC activators. Identification of the PKC isozymes that respond to aFGF and TGF-beta 1 and their subcellular localization may provide a molecular basis for the divergent cardiac functions mediated by these two growth factors.
Disatnik
M H
MH
Department of Molecular Pharmacology, School of Medicine, Stanford University, CA 94305, USA.
Jones
S N
SN
Mochly-Rosen
D
D
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology; D004789:Enzyme Activation; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D007527:Isoenzymes; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D011493:Protein Kinase C / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007527:Isoenzymes; D016212:Transforming Growth Factor beta; D016220:Fibroblast Growth Factor 1; D011493:Protein Kinase C