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

FEBS Letters

Peres, Christine¹  Salles, Jean-Pierre¹  Perret, Bertrand¹  Raynal, Patrick¹  Yart, Armelle¹ 

[1] INSERM U563, Department of Lipoproteins and Lipid Mediators, IFR 30, Hôpital Purpan, 31059 Toulouse, France

关键词: Lysophosphatidic acid;    Phosphoinositide 3-kinase;    Lipid raft;    Cholesterol depletion;    EGFR;    epidermal growth factor receptor;    LPA;    lysophosphatidic acid;    MAPK;    mitogen-activated protein kinase;    MβCD;    methyl-β-cyclodextrin;    PtdIns(3;    4)P2;    phosphatidylinositol 3;    4-bisphosphate;    PtdIns(4;    5)P2;    phosphatidylinositol 4;    5-bisphosphate;    PtdIns(3;    4;    5)P2;    phosphatidylinositol 3;    4;    5-trisphosphate;    PKB;    protein kinase B;   

DOI  :  10.1016/S0014-5793(02)03832-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Methyl-β-cyclodextrin (MβCD) 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 MβCD. MβCD 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 MβCD-treated cells, suggesting that these microdomains contribute to LPA signalling by compartmentalising component(s) of the PI3K pathway.

【 授权许可】

Unknown