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J. Biol. Chem., Vol. 278, Issue 13, 11561-11569, March 28, 2003
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From the Lipid rafts/caveolae are found to be essential
for insulin-like growth factor (IGF)-1 receptor signaling during 3T3-L1
preadipocyte differentiation induction. In 3T3-L1 cells, IGF-1 receptor
is located in lipid rafts/caveolae of the plasma membrane and can directly interact with caveolin-1, the major protein component in
caveolae. Disruption of lipid rafts/caveolae by depleting cellular cholesterol with cholesterol-binding reagent,
Lipid Rafts/Caveolae Are Essential for
Insulin-like Growth Factor-1 Receptor Signaling during 3T3-L1
Preadipocyte Differentiation Induction*
§,§,§¶
State Laboratory of Molecular Biology and
§ Institute of Biochemistry and Cell Biology, Shanghai
Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, China
-methylcyclodextrin or
filipin, blocks the IGF-1 receptor signaling in 3T3-L1 preadipocyte. Both hormonal induced adipocyte differentiation and mitotic clonal expansion are inhibited by lipid rafts/caveolae disruption. However, a
nonspecific lipid binding reagent, xylazine, does not affect adipocyte
differentiation or mitotic clonal expansion. Further studies indicate
that lipid rafts/caveolae are required only for IGF-1 receptor
downstream signaling and not the activation of receptor itself by
ligand. Thus, our results suggest that localization in lipid
rafts/caveolae and association with caveolin enable IGF-1 receptor to
have a close contact with downstream signal molecules recruited into
lipid rafts/caveolae and transmit the signal through these signal
molecule complexes.
*
This work was supported by Chinese National Nature Sciences
Foundation Research Grants 39825107 and 30270336, Chinese Academy of
Sciences Grant KSCX2-SW-203, and Ministry of Science and Technology Grant 2002CB513000.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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