Modulation of phosphoinositide 3-kinase activation by cholesterol level suggests a novel positive role for lipid rafts in lysophosphatidic acid signalling |
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Authors: | Peres Christine Yart Armelle Perret Bertrand Salles Jean Pierre Raynal Patrick |
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Affiliation: | INSERM U563, Department of Lipoproteins and Lipid Mediators, IFR 30, H?pital Purpan, 31059 Toulouse, France. |
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Abstract: | 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. |
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