Regulation of phospholipase C-β activity by phosphatidic acid:: Isoform dependence, role of protein kinase C, and G protein subunit

被引：24

作者：

Litosch, I ^{[1
]}

机构：

[1] Univ Miami, Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33101 USA

来源：

BIOCHEMISTRY | 2003年 / 42卷 / 06期

关键词：

D O I：

10.1021/bi026414h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphatidic acid (PA) stimulates phospholipase C-beta(1) (PLC-beta(1)) activity and promotes G protein stimulation of PLC-beta(1) activity. The isoform dependence for PA regulation of PLC-beta activity as well as the role of PA in modulating regulation of PLC-beta activity by protein kinase C (PKC) and G protein subunits was determined. As compared to PLC-beta(1), the phospholipase C-beta(3) (PLC-beta(3)) isoform was less sensitive to PA, requiring greater than 15 mol % PA for stimulation. PLC-beta(3) bound weakly to PA. PKC had little effect on PA stimulation of PLC-beta(3) activity. PKC, however, inhibited PA stimulation of PLC-beta(1) activity through a mechanism dependent on the mol % PA. Stimulation by 7.5 mol % PA was completely inhibited by PKC. Increasing the PA and Ca2+ concentration attenuated PKC inhibition. The binding of PLC-P, to PA containing phospholipid vesicles was also reduced by PKC, in a manner dependent on the mol % PA. PA increased the stimulation of PLC-beta(1) activity by Galphaq but had little effect on the stimulation by betagamma subunits. These results demonstrate that PA stimulation of PLC-beta activity is tightly regulated, suggesting the existence of a distinct PA binding region in PLC-beta(1). PA may be an important component of a receptor mediated signaling mechanism that determines PLC-beta(1) activation.

引用

页码：1618 / 1623

页数：6

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