HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knutson, V. P. Articles by Lane, M. D. Search for Related Content PubMed PubMed Citation Articles by Knutson, V. P. Articles by Lane, M. D. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 258, Issue 20, 12139-12142, 10, 1983

Rapid, reversible internalization of cell surface insulin receptors. Correlation with insulin-induced down-regulation

VP Knutson, GV Ronnett and MD Lane

Chronic treatment of 3T3-C2 fibroblasts with insulin causes the slow (t1/2 = 3-4 h) down-regulation of cellular insulin receptor to a new steady state level by accelerating receptor decay (Knutson, V.P., Ronnett, G.V., and Lane, M.D. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2822-2826). In the present investigation, the synthesis and turnover of the receptor during the transition to the down-regulated state was examined by the heavy isotope density-shift method. It was observed that within two h after insulin addition, receptor decay increased abruptly for several hours then gradually declined until the "down- regulated" rate was achieved. The abrupt increase in receptor decay induced by insulin was preceded by a more rapid (t1/2 less than or equal to 10 min) translocation of cell surface receptor to an "intracellular" trypsin-resistant compartment. Thus, upon exposure to ligand, insulin receptor rapidly redistributes from the cell surface to an intracellular compartment, without an initial net loss of cellular receptors. The translocation process was rapidly reversed (t1/2 less than or equal to 20 min) upon removal of insulin. With prolonged exposure to insulin, the initial rapid translocation of receptor was followed by a slower inactivation of receptor apparently in the intracellular compartment. Cycloheximide, which lengthens receptor half- life by blocking a step in receptor inactivation, had no effect on receptor internalization. Internalization of insulin receptor and its bound ligand were, however, rapidly (less than 10 min) blocked by phenylarsine oxide. These results support the following sequence of events. Upon exposure to ligand, insulin receptors are translocated from the cell surface to an intracellular site which results in accelerated receptor decay and ultimately to a lower steady state cellular receptor level.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. J. Ramos, P. R. Langlais, D. Hu, L. Q. Dong, and F. Liu Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1262 - E1266. [Abstract] [Full Text] [PDF]

				A. H. A. Clayton, F. Walker, S. G. Orchard, C. Henderson, D. Fuchs, J. Rothacker, E. C. Nice, and A. W. Burgess Ligand-induced Dimer-Tetramer Transition during the Activation of the Cell Surface Epidermal Growth Factor Receptor-A Multidimensional Microscopy Analysis J. Biol. Chem., August 26, 2005; 280(34): 30392 - 30399. [Abstract] [Full Text] [PDF]

				F. Walker, S. G. Orchard, R. N. Jorissen, N. E. Hall, H.-H. Zhang, P. A. Hoyne, T. E. Adams, T. G. Johns, C. Ward, T. P. J. Garrett, et al. CR1/CR2 Interactions Modulate the Functions of the Cell Surface Epidermal Growth Factor Receptor J. Biol. Chem., May 21, 2004; 279(21): 22387 - 22398. [Abstract] [Full Text] [PDF]

				S. Tanabe, Y. Shimohigashi, Y. Nakayama, T. Makino, T. Fujita, T. Nose, G. Tsujimoto, T. Yokokura, M. Naito, T. Tsuruo, et al. In Vivo and In Vitro Evidence of Blood-Brain Barrier Transport of a Novel Cationic Arginine-Vasopressin Fragment 4-9 Analog J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 561 - 568. [Abstract] [Full Text]