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Functional consequence of targeting protein kinase B/Akt to GLUT4 vesicles

Pierre-Henri Ducluzeau^*, Laura M. Fletcher^*, Gavin I. Welsh and Jeremy M. Tavaré

Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK
^* These authors contributed equally to this work

Author for correspondence (e-mail: j.tavare{at}bris.ac.uk )

Accepted 14 May 2002

We have investigated the role of protein kinase B (Akt) in the insulin-stimulated translocation of vesicles containing the insulin-responsive isoform of glucose transporter (GLUT4) to the plasma membrane of adipocytes. Previous reports have suggested that protein kinase B can bind to intracellular GLUT4 vesicles in an insulin-dependent manner, but the functional consequence of this translocation is not known. In this study we have artificially targeted constitutively active and kinase-inactive mutants of protein kinase B to intracellular GLUT4 vesicles by fusing them with the N-terminus of GLUT4 itself. We examined the effect of these mutants on the insulin-dependent translocation of the insulin-responsive amino peptidase IRAP (a bona fide GLUT4-vesicle-resident protein). A kinase-inactive protein kinase B targeted to GLUT4 vesicles was an extremely effective dominant-negative inhibitor of insulin-stimulated IRAP translocation to the plasma membrane. By contrast, a kinase-inactive protein kinase B expressed in the cytoplasm did not have an effect. The results suggest that protein kinase B has an important functional role at, or in the vicinity of, GLUT4 vesicles in the insulin-dependent translocation of those vesicles to the plasma membrane of adipocytes.

Key words: Insulin, GLUT4, Signalling, Protein kinase B/Akt, Adipocytes

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