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Selective activation of protein kinase C isoforms by v-Src
Q Zang1, P Frankel, D A Foster
1Institute for Biomolecular Structure and Function, Hunter College, City University of New York, New York 10021, USA.
Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|November 1, 1995
Summary
v-Src transformation selectively activates Protein Kinase C (PKC) alpha and delta isoforms in fibroblasts. This suggests a role for these specific PKC isoforms in cell mitogenesis and transformation, indicating complex activation mechanisms beyond simple diacylglycerol levels.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Protein Kinase C (PKC) is a family of 11+ isoforms involved in cellular signaling.
- PKC activation is often indicated by membrane association.
- v-Src transformation is linked to intracellular signals regulating cell growth and transformation.
Purpose of the Study:
- To investigate the activation patterns of specific PKC isoforms (alpha, delta, epsilon, zeta) in v-Src-transformed fibroblasts.
- To determine if PKC activation correlates with membrane association in transformed cells.
- To elucidate the role of different PKC isoforms in v-Src-mediated cell transformation.
Main Methods:
- Detection of four PKC isoforms (alpha, delta, epsilon, zeta) in murine and rat fibroblasts.
- Analysis of Ca(2+)-dependent and independent membrane association of PKC isoforms in parental and v-Src-transformed cells.
- Assessment of PKC epsilon responsiveness to exogenous diacylglycerol (DG) and phorbol ester.
Main Results:
- PKC alpha showed Ca(2+)-dependent membrane association in v-Src-transformed cells.
- PKC delta, a Ca(2+)-independent isoform, was preferentially membrane-associated in v-Src-transformed cells.
- PKC epsilon activation was not observed despite responsiveness to DG, suggesting complex regulation.
- PKC zeta showed inconclusive changes in membrane association.
Conclusions:
- v-Src selectively activates PKC alpha and delta isoforms.
- The differential activation of PKC delta and epsilon implies complex regulatory mechanisms beyond DG levels.
- Activated PKC alpha and delta isoforms likely play a role in v-Src-induced mitogenesis and cell transformation.