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Vol. 15, Issue 10, 4406-4415, October 2004
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* Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021;
Training Program in Chemical Biology, Weill Medical College of Cornell University, New York, NY 10021
Submitted April 22, 2004;
Revised July 2, 2004;
Accepted July 6, 2004
Monitoring Editor: Juan S. Bonifacino
Insulin maintains whole body blood glucose homeostasis, in part, by regulating the amount of the GLUT4 glucose transporter on the cell surface of fat and muscle cells. Insulin induces the redistribution of GLUT4 from intracellular compartments to the plasma membrane, by stimulating a large increase in exocytosis and a smaller inhibition of endocytosis. A considerable amount is known about the molecular events of insulin signaling and the complex itinerary of GLUT4 trafficking, but less is known about how insulin signaling is transmitted to GLUT4 trafficking. Here, we show that the AS160 RabGAP, a substrate of Akt, is required for insulin stimulation of GLUT4 exocytosis. A dominant-inhibitory mutant of AS160 blocks insulin stimulation of exocytosis at a step before the fusion of GLUT4-containing vesicles with the plasma membrane. This mutant, however, does not block insulin-induced inhibition of GLUT4 endocytosis. These data support a model in which insulin signaling to the exocytosis machinery (AS160 dependent) is distinct from its signaling to the internalization machinery (AS160 independent).
Corresponding author: E-mail address: temcgraw{at}med.cornell.edu.
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|
|
|
|
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|
|
|
|
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|
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|
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|
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|
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|
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|
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|
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