Research

AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane


Reference:

Koumanov, F., Richardson, J. D., Murrow, B. A. and Holman, G. D., 2011. AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane. Journal of Biological Chemistry, 286 (19), pp. 16574-16582.

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    Official URL:

    http://dx.doi.org/10.1074/jbc.M111.226092

    Abstract

    AS160 (TBC1D4) is a known Akt substrate that is phosphorylated downstream of insulin action and that leads to regulated traffic of GLUT4. As GLUT4 vesicle fusion with the plasma membrane is a highly regulated step in GLUT4 traffic, we investigated whether AS160 and 14-3-3 interactions are involved in this process. Fusion was inhibited by a human truncated AS160 variant that encompasses the first N-terminal phosphotyrosine-binding (PTB) domain, by either of the two N-terminal PTB domains, and by a tandem construct of both PTB domains of rat AS160. We also found that in vitro GLUT4 vesicle fusion was strongly inhibited by the 14-3-3-quenching inhibitors R18 and fusicoccin. To investigate the mode of interaction of AS160 and 14-3-3, we examined insulin-dependent increases in the levels of these proteins on GLUT4 vesicles. 14-3-3 gamma was enriched on insulin-stimulated vesicles, and its binding to AS160 on GLUT4 vesicles was inhibited by the AS160 tandem PTB domain construct. These data suggest a model for PTB domain action on GLUT4 vesicle fusion in which these constructs inhibit insulin-stimulated 14-3-3 gamma interaction with AS160 rather than AS160 phosphorylation.

    Details

    Item Type Articles
    CreatorsKoumanov, F., Richardson, J. D., Murrow, B. A. and Holman, G. D.
    DOI10.1074/jbc.M111.226092
    DepartmentsFaculty of Science > Biology & Biochemistry
    Faculty of Humanities & Social Sciences > Health
    Publisher StatementKoumanov_JBC_2011.pdf: This research was originally published in The Journal of Biological Chemistry. Koumanov, F., Richardson, J. D., Murrow, B. A. and Holman, G. D., 2011. AS160 Phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane. Journal of Biological Chemistry, 286 (19), pp. 16574-16582. © the American Society for Biochemistry and Molecular Biology.
    RefereedYes
    StatusPublished
    ID Code24121

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