Modulation of phosphoinositide 3-kinase activation by cholesterol level suggests a novel positive role for lipid rafts in lysophosphatidic acid signalling

被引：51

作者：

Peres, C ^{[1
]}

Yart, A ^{[1
]}

Perret, B ^{[1
]}

Salles, JP ^{[1
]}

Raynal, P ^{[1
]}

机构：

[1] Hop Purpan, INSERM, U563, Dept Lipoprot & Lipid Mediators, F-31059 Toulouse, France

来源：

FEBS LETTERS | 2003年 / 534卷 / 1-3期

关键词：

lysophosphatidic acid; phosphoinositide; 3-kinase; lipid raft; cholesterol depletion;

D O I：

10.1016/S0014-5793(02)03832-2

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：

Methyl-beta-cyclodextrin (MbetaCD) was used to explore a role for cholesterol-enriched plasma membrane microdomains in coupling lysophosphatidic acid (LPA) stimulation to phosphoinositide 3-kinase (PI3K) activation. Cholesterol depletion strongly inhibited the production of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate in Vero cells stimulated with LPA. In agreement, the phosphorylation of Akt/protein kinase B, but not of Erk kinases, was suppressed by MbetaCD. MbetaCD did not interfere with the overall phospholipid metabolism, and its effects were reversed in cholesterol add-back experiments. Finally, PI3K was detected in lipid rafts prepared from control but not MbetaCD-treated cells, suggesting that these microdomains contribute to LPA signalling by compartmentalising component(s) of the PI3K pathway. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：164 / 168

页数：5

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