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Insulin induces phosphatidylinositol‐3‐phosphate formation through TC10 activation
Author(s) -
Maffucci Tania,
Brancaccio Anna,
Piccolo Enza,
Stein Robert C.,
Falasca Marco
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg402
Subject(s) - phosphatidylinositol , glut4 , biology , microbiology and biotechnology , endosome , lipid raft , chromosomal translocation , insulin receptor , internalization , glucose transporter , signal transduction , insulin , pleckstrin homology domain , intracellular , biochemistry , receptor , insulin resistance , endocrinology , gene
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‐P 3 ) 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.