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J Biol Chem, Vol. 273, Issue 39, 25450-25457, September 25, 1998
From the Department of Physiology and Biophysics, University of
Iowa, Iowa City, Iowa 52242-1109
To examine the role of clathrin-coated vesicle
endocytosis in insulin receptor signaling and GLUT4 trafficking, we
used recombinant adenovirus to express a dominant interfering mutant of
dynamin (K44A/dynamin) in 3T3L1 adipocytes. Functional expression of
K44A/dynamin, as measured by inhibition of transferrin receptor
internalization, did not affect insulin-stimulated insulin receptor
autophosphorylation, Shc tyrosine phosphorylation, or mitogen-activated
protein kinase activation. Although the tyrosine phosphorylation of
insulin receptor substrate-1 was slightly reduced, correlating with a
25% decrease in insulin receptor substrate-1-associated
phosphatidylinositol 3-kinase activity, insulin-stimulated Akt kinase
activation was unaffected. In contrast, expression of K44A/dynamin
resulted in the cell-surface accumulation of GLUT4 under basal
conditions and an inhibition of GLUT4 endocytosis without affecting
insulin-stimulated GLUT4 exocytosis. These data demonstrate that
disruption of clathrin-mediated endocytosis does not significantly
perturb insulin receptor signal transduction pathways. Furthermore,
K44A/dynamin expression causes an accumulation of GLUT4 at the cell
surface, suggesting that GLUT4 vesicles exist in at least two distinct
intracellular compartments, one that undergoes continuous recycling and
a second that is responsive to insulin.
Expression of a Dominant Interfering Dynamin Mutant in 3T3L1
Adipocytes Inhibits GLUT4 Endocytosis without Affecting Insulin
Signaling
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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J. B. Knight, K. T. Cao, G. V. Gibson, and A. L. Olson Expression of a Prenylation-Deficient Rab4 Interferes with Propagation of Insulin Signaling through Insulin Receptor Substrate-1 Endocrinology, January 1, 2000; 141(1): 208 - 218. [Abstract] [Full Text] [PDF]
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D. Duan, Q. Li, A. W. Kao, Y. Yue, J. E. Pessin, and J. F. Engelhardt Dynamin Is Required for Recombinant Adeno-Associated Virus Type 2 Infection J. Virol., December 1, 1999; 73(12): 10371 - 10376. [Abstract] [Full Text]
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C. A. Millar, K. A. Powell, G. R. X. Hickson, M.-F. Bader, and G. W. Gould Evidence for a Role for ADP-ribosylation Factor 6 in Insulin-stimulated Glucose Transporter-4 (GLUT4) Trafficking in 3T3-L1 Adipocytes J. Biol. Chem., June 18, 1999; 274(25): 17619 - 17625. [Abstract] [Full Text] [PDF]
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A. W. Kao, Y. Noda, J. H. Johnson, J. E. Pessin, and A. R. Saltiel Aldolase Mediates the Association of F-actin with the Insulin-responsive Glucose Transporter GLUT4 J. Biol. Chem., June 18, 1999; 274(25): 17742 - 17747. [Abstract] [Full Text] [PDF]
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J. L. DeGraff, A. W. Gagnon, J. L. Benovic, and M. J. Orsini Role of Arrestins in Endocytosis and Signaling of alpha 2-Adrenergic Receptor Subtypes J. Biol. Chem., April 16, 1999; 274(16): 11253 - 11259. [Abstract] [Full Text] [PDF]
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J. E. Pessin, D. C. Thurmond, J. S. Elmendorf, K. J. Coker, and S. Okada Molecular Basis of Insulin-stimulated GLUT4 Vesicle Trafficking. LOCATION! LOCATION! LOCATION! J. Biol. Chem., January 29, 1999; 274(5): 2593 - 2596. [Full Text] [PDF]
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S. Shigematsu, S. L. Miller, and J. E. Pessin Differentiated 3T3L1 Adipocytes Are Composed of Heterogenous Cell Populations with Distinct Receptor Tyrosine Kinase Signaling Properties J. Biol. Chem., April 27, 2001; 276(18): 15292 - 15297. [Abstract] [Full Text] [PDF]
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D. Li, V. K. Randhawa, N. Patel, M. Hayashi, and A. Klip Hyperosmolarity Reduces GLUT4 Endocytosis and Increases Its Exocytosis from a VAMP2-independent Pool in L6 Muscle Cells J. Biol. Chem., June 15, 2001; 276(25): 22883 - 22891. [Abstract] [Full Text] [PDF]
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D. L. Silver, N. Wang, X. Xiao, and A. R. Tall High Density Lipoprotein (HDL) Particle Uptake Mediated by Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL Cholesterol from Protein and Polarized Cholesterol Secretion J. Biol. Chem., June 29, 2001; 276(27): 25287 - 25293. [Abstract] [Full Text] [PDF]
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J. Huang, T. Imamura, and J. M. Olefsky Insulin can regulate GLUT4 internalization by signaling to Rab5 and the motor protein dynein PNAS, November 6, 2001; 98(23): 13084 - 13089. [Abstract] [Full Text] [PDF]
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T.-X. Sun, A. Van Hoek, Y. Huang, R. Bouley, M. McLaughlin, and D. Brown Aquaporin-2 localization in clathrin-coated pits: inhibition of endocytosis by dominant-negative dynamin Am J Physiol Renal Physiol, June 1, 2002; 282(6): F998 - F1011. [Abstract] [Full Text] [PDF]
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