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• W2116735445 endingPage "5503" @default.
• W2116735445 startingPage "5497" @default.
• W2116735445 abstract "Caveolae are lipid raft microdomains that regulate endocytosis and signal transduction. IGF-I receptor (IGF-IR) localizes in caveolae and tyrosine phosphorylates caveolin 1, supporting a role for these subcellular regions in the compartmentalization of IGF-I signaling. Src homology 2/alpha-collagen related protein (Shc) is the main mediator of IGF-I mitogenic action, coupling IGF-IR phosphorylation to Ras-MAPK activation. Here we show that IGF-I induces Shc tyrosine phosphorylation in the caveolae with a time course significantly different from that observed in the nonraft cellular fractions. In the same time, IGF-I recruits growth factor receptor bound protein 2 (Grb2) to caveolae and activates p42/p44 MAPKs in these microdomains. Src family kinases regulate IGF-I action through an Shc-dependent mechanism. In R-IGF-IRWT cells, IGF-I causes Fyn enrichment in the caveolae with a time course consistent with Shc phosphorylation and Grb2 recruitment in these regions. Finally, we have observed that after IGF-I stimulation, IGF-IR and Fyn colocalize in lipid raft caveolin 1-enriched microdomains. As insulin and IGF-I share common substrates, the effect of insulin on these cellular processes was measured. Here we show that insulin also induces Shc phosphorylation and Grb2 recruitment to caveolae, but with a significantly different time course compared with IGF-I. Our results suggest that 1) IGF-I causes the colocalization of signaling proteins in caveolae through a phosphorylation-regulated mechanism; and 2) the time course of phosphorylation and recruitment of substrates in caveolae by insulin receptor and IGF-IR could determine the specific actions of these receptors." @default.
• W2116735445 created "2016-06-24" @default.
• W2116735445 creator A5008248272 @default.
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• W2116735445 date "2003-12-01" @default.
• W2116735445 modified "2023-10-05" @default.
• W2116735445 title "Specificity of Insulin-Like Growth Factor I and Insulin on Shc Phosphorylation and Grb2 Recruitment in Caveolae" @default.
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• W2116735445 doi "https://doi.org/10.1210/en.2003-0417" @default.
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