Phosphatidylinositol 3-kinase is required for insulin-stimulated tyrosine phosphorylation of Shc in 3T3-L1 adipocytes.

The Journal of Biological Chemistry
Satoshi UgiJerrold M Olefsky

Abstract

The interactions between the phosphatidylinositol 3-kinase (PI 3-kinase) and Ras/MAPK kinase pathways have been the subject of considerable interest. In the current studies, we find that epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) lead to rapid phosphorylation of Shc (maximum at 1-2 min), whereas insulin-mediated Shc phosphorylation is relatively delayed (maximum at 5-10 min), suggesting that an intermediary step may be necessary for insulin stimulation of Shc phosphorylation. The Src homology-2 (SH2) domain of Shc is necessary for PDGF- and EGF-mediated Shc phosphorylation, whereas the phosphotyrosine binding (PTB) domain is critical for the actions of insulin. Because the Shc PTB domain can interact with phospholipids, we postulated that PI 3-kinase might be a necessary intermediary step facilitating insulin-stimulated phosphorylation of Shc. In support of this, we found that the PI 3-kinase inhibitors, wortmannin and LY294002, blocked insulin-stimulated but not EGF- or PDGF-stimulated Shc phosphorylation. Furthermore, overexpression of a dominant negative PI 3-kinase construct (p85N-SH2) blocked insulin, but not EGF- or PDGF-induced Shc phosphorylation. All three growth factors cause localization ...Continue Reading

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Citations

May 24, 2003·Trends in Molecular Medicine·Sally Purdom, Qin M Chen
Jul 11, 2006·The Journal of Clinical Investigation·Clay F Semenkovich
Mar 11, 2003·Reproductive Biomedicine Online·Izhar Ben-Shlomo
Feb 1, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabine UhlesIngo B Leibiger

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