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| Subject Categories: Membranes & Transport | Signal Transduction |
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| The EMBO Journal
(2003) 22, 4178–4189, doi:10.1093/emboj/cdg402 |
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| Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation |
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| Tania Maffucci1, Anna Brancaccio1, Enza Piccolo2, Robert C. Stein3 and Marco Falasca1 |
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1 The Sackler Institute, University College London, 5 University Street, London WC1E 6JJ, UK 2 Department of Oncology and Neurosciences, Università G. D'Annunzio, Via dei Vestini 1, 66100 Chieti, Italy 3 The Ludwig Institute for Cancer Research, University College London, 91 Riding House Street, London W1P 8BT, UK To whom correspondence should be addressed Marco Falasca, m.falasca@ucl.ac.uk Received 17 January 2003; Revised 25 June 2003; Accepted 26 June 2003. |
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| Abstract |
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| Phosphatidylinositol-3-phosphate (PtdIns-3-P) is considered as a lipid constitutively present on endosomes; it does not seem to have a dynamic role in signalling. In contrast, phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) plays a crucial role in different signalling pathways including translocation of the glucose transporter protein GLUT4 to the plasma membrane upon insulin receptor activation. GLUT4 translocation requires activation of two distinct pathways involving phosphatidylinositol 3-kinase (PI 3-K) and the small GTP-binding protein TC10, respectively. The contribution of each pathway remains to be elucidated. Here we show that insulin specifically induces the formation of PtdIns-3-P in insulin- responsive cells. The insulin-mediated formation of PtdIns-3-P occurs through the activation of TC10 at the lipid rafts subdomain of the plasma membrane. Exogenous PtdIns-3-P induces the plasma membrane translocation of both overexpressed and endogenous GLUT4. These data indicate that PtdIns-3-P is specifically produced downstream from insulin-mediated activation of TC10 to promote the plasma membrane translocation of GLUT4. These results give a new insight into the intracellular role of PtdIns-3-P and shed light on some aspects of insulin signalling so far not completely understood. |
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| Keywords: GLUT4, insulin, phosphatidylinositol 3-kinase, phosphatidylinositol-3-phosphate, TC10 |
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