Regulation of phospholipase C isozymes by Ras superfamily GTPases

被引:100
作者
Harden, TK [1 ]
Sondek, J
机构
[1] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
关键词
phosphoinositide; PLC-beta; PLC-epsilon; Rac; Rho;
D O I
10.1146/annurev.pharmtox.46.120604.141223
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The physiological effects of many extracellular stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid-signaling pathways. These signaling responses include the classically described conversion of PtdIns(4,5)P-2 to the Ca2+-mobilizing second messenger Ins(1,4,5)P-3 and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. Here we discuss how the family of PLCs elaborates a minimal catalytic core typified by PLC-delta to confer multiple modes of regulation on their phospholipase activities. Although PLC-dependent signaling is prominently regulated by direct interactions with heterotrimeric G proteins or tyrosine kinases, the existence of at least 13 divergent PLC isozymes promises a diverse repertoire of regulatory mechanisms for this class of important signaling proteins. We focus here on the recently realized and extensive regulation of inositol lipid signaling by Ras superfamily GTPases directly acting on PLC isozymes and conclude by considering the biological and pharmacological ramifications of this regulation.
引用
收藏
页码:355 / 379
页数:33
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