Selective activation of protein kinase C isoforms by v-Src.
Protein kinase C (PKC) is a gene family consisting of no less than 11 distinct isoforms. In both murine and rat fibroblasts, we detected expression of four PKC isoforms: the conventional PKC alpha, the novel PKCs delta and epsilon, and the atypical PKC zeta. With the conventional and novel PKC isoforms, membrane association has been used to show PKC activation. In cells transformed by v-Src, there was a Ca(2+)-dependent increase in membrane association of the alpha isoform relative to the nontransformed parental cells. The zeta isoform had a slightly increased membrane association in murine fibroblasts transformed by v-Src but not in rat fibroblasts transformed by v-Src. However, since it is not clear whether cellular distribution of zeta isoform correlates with activation, the data are inconclusive with regard to this isoform. Interestingly, of the Ca(2+)-independent PKC isoforms delta and epsilon, only the delta isoform was preferentially associated with membrane fractions in v-Src-transformed cells. The lack of PKC epsilon activation was not due to lack of responsiveness to diacylglycerol (DG), since exogenously supplied DG and phorbol ester were both able to induce membrane association of PKC epsilon. Thus, the differential activation of the delta and epsilon isoforms by v-Src suggests a more complex mechanism for the activation of the novel Ca(2+)-independent PKC isoforms, involving more than simply elevating DG levels. Since PKC has been implicated in the intracellular signals activated by v-Src that lead to transformation, the selective activation of PKC alpha and delta suggests a role in mitogenesis and transformation for these PKC isoforms.
Zang
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Q
Institute for Biomolecular Structure and Function, Hunter College, City University of New York, New York 10021, USA.
Frankel
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P
Foster
D A
DA
D016475:3T3 Cells / Q000166:cytology; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D002458:Cell Fractionation; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D014170:Transformation, Genetic
D004075:Diglycerides; D007527:Isoenzymes; D008565:Membrane Proteins; C497259:Prkcd protein, mouse; C497260:Prkcd protein, rat; D015688:Oncogene Protein pp60(v-src); C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D002118:Calcium