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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Peres C,Yart A,Perret B,Salles JP,Raynal P

doi

10.1016/s0014-5793(02)03832-2

keywords:

subject

Has Abstract

pub_date

2003-01-16 00:00:00

pages

164-8

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302038322

journal_volume

534

pub_type

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