Author： Kiss Z. Petrovics G. Olàh Z. Lehel C. Anderson W.B.
Publisher： Elsevier
ISSN： 0003-9861
Source： Archives of Biochemistry and Biophysics, Vol.363, Iss.1, 1999-03, pp. : 121-128
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Abstract
In fibroblasts, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) stimulates phospholipase D (PLD)-mediated hydrolysis of both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) by PKC-α-mediated nonphosphorylating and phosphorylating mechanisms. Here we have used NIH 3T3 fibroblasts overexpressing holo PKC-ɛ and its regulatory, catalytic, and zinc finger domain fragments to determine if this isozyme also regulates PLD activity. Overexpression of holo PKC-ɛ inhibited the stimulatory effects of PMA (5–100 nM) on both PtdCho and PtdEtn hydrolysis. Overexpression of PKC-ɛ also was found to inhibit platelet-derived growth factor-induced PLD activity. Expression of the catalytic unit of PKC-ɛ had no effect on PMA-induced PLD activity. In contrast, expression of both the regulatory domain fragment and the zinc finger domain of PKC-ɛ resulted in significant inhibition of PMA-stimulated PtdCho and PtdEtn hydrolysis. Interestingly, although PKC-α also mediates the stimulatory effect of PMA on the synthesis of PtdCho by a phosphorylation mechanism, overexpression of holo PKC-ɛ or its regulatory domain fragments did not affect PMA-induced PtdCho synthesis. These results indicate that the PKC-ɛ system can act as a negative regulator of PLD activity and that this inhibition is mediated by its regulatory domain.
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