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Modulation of phosphoinositide 3‐kinase activation by cholesterol level suggests a novel positive role for lipid rafts in lysophosphatidic acid signalling
Author(s) -
Peres Christine,
Yart Armelle,
Perret Bertrand,
Salles Jean-Pierre,
Raynal Patrick
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03832-2
Subject(s) - lysophosphatidic acid , phosphatidylinositol , lipid raft , microbiology and biotechnology , pi3k/akt/mtor pathway , kinase , phosphorylation , phosphoinositide 3 kinase , protein kinase b , signal transduction , mapk/erk pathway , biology , chemistry , biochemistry , receptor
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.