The trimeric GTP-binding protein (G(q)/G11) α subunit is required for insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes

Makoto Kanzaki, Robert T. Watson, Nikolai O. Artemyev, Jeffrey E. Pessin

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

To investigate the potential role of trimeric GTP-binding proteins regulating GLUT4 translocation in adipocytes, wild type and constitutively active G(q) (G(q)/Q209L), G(i) (G(i)/Q205L), and G(s) (G(s)/Q227L) α subunit mutants were expressed in 3T3L1 adipocytes. Although expression of neither the wild type nor G(i)/Q205L and G(s)/Q227L α subunit mutants had any effect on the basal or insulin-stimulated translocation of a co-expressed GLUT4- enhanced green fluorescent protein (EGFP) fusion protein, expression of G(q)/Q209L resulted in GLUT4-EGFP translocation in the absence of insulin. In contrast, microinjection of an inhibitory G(q)/G11 α subunit-specific antibody but not a G(i) or G(s) α subunit antibody prevented insulin- stimulated endogenous GLUT4 translocation. Consistent with a required role for GTP-bound G(q)/G11, expression of the regulators of G protein signaling (RGS4 and RGS16) also attenuated insulin-stimulated GLUT4-EGFP translocation. To assess the relationship between G(q)/G11 function with the phosphatidylinositol 3-kinase dependent pathway, expression of a dominant- interfering p85 regulatory subunit, as well as wortmannin treatment inhibited insulin-stimulated but not G(q)/Q209L-stimulated GLUT4-EGFP translocation. Furthermore, G(q)/Q209L did not induce the in vivo accumulation of phosphatidylinositol-3,4,5-trisphosphate (PIP3), whereas expression of the RGS proteins did not prevent the insulin-stimulated accumulation of PIP3. Together, these data demonstrate that insulin stimulation of GLUT4 translocation requires at least two independent signal transduction pathways, one mediated through the phosphatidylinositol 3-kinase and another through the trimeric GTP-binding proteins G(q) and/or G11.

Original languageEnglish (US)
Pages (from-to)7167-7175
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number10
DOIs
StatePublished - Mar 10 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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