This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balbis, A. Articles by Posner, B. I. Search for Related Content PubMed PubMed Citation Articles by Balbis, A. Articles by Posner, B. I.

Compartmentalization and Insulin-Induced Translocations of Insulin Receptor Substrates, Phosphatidylinositol 3-Kinase, and Protein Kinase B in Rat Liver¹

Polypeptide Hormone Laboratory and Department of Anatomy and Cell Biology (J.J.M.B.), McGill University, Montréal, Québec, Canada H3A 2B2

Address all correspondence and requests for reprints to: Dr. B. I. Posner, Polypeptide Hormone Laboratory, Strathcona Anatomy and Dentistry Building, 3640 University Street, Room W3.15, Montréal, Québec, Canada H3A 2B2. E-mail: mc85{at}musica.mcgill.ca

Physiological doses of insulin in rats resulted in a rapid redistribution of key signaling proteins between subcellular compartments in rat liver. In plasma membranes (PM) and microsomes, insulin induced a rapid decrease in insulin receptor substrate-1/2 (IRS1/2) within 30 sec and an increase in these proteins in endosomes (EN) and cytosol. The level of p85 in PM increased 2.3-fold at 30 sec after insulin stimulation followed by a decrease at 2 min. In this interval, 60–85% and 10–20% of p85 in PM was associated with IRS1 and IRS2, respectively. Thus, in PM, IRS1/2 accounts for almost all of the protein involved in phosphatidylinositol 3-kinase activation. In ENs insulin induced a maximal increase of 40% in p85 recruitment. As in PM, almost all p85 was associated with IRS1/2. The greater level of p85 recruitment to PM was associated with a higher level of insulin-induced recruitment of Akt1 to this compartment (4.0-fold in PM vs. 2.4-fold in EN). There was a close correlation between Akt1 activity and Akt1 phosphorylation at Thr³⁰⁸ and Ser⁴⁷³ in PM and cytosol. However, in ENs the level of Akt1 activity per unit of phosphorylated Akt1 was significantly greater than in PM, indicating that in addition to phosphorylation, another factor(s) modulates Akt1 activation by insulin in rat liver. Our results demonstrate that activation of the insulin receptor kinase and modulation of key components of the insulin signaling cascade occur at the cell surface and within the endosomal system. These data provide further support for the role of the endocytic process in cell signaling.

This article has been cited by other articles:

				C. Le Foll, C. Corporeau, V. Le Guen, J.-P. Gouygou, J.-P. Berge, and J. Delarue Long-chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from phosphatidylinositol 3'-kinase activity in rats Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1223 - E1230. [Abstract] [Full Text] [PDF]

				C. Corporeau, C. L. Foll, M. Taouis, J.-P. Gouygou, J.-P. Berge, and J. Delarue Adipose tissue compensates for defect of phosphatidylinositol 3'-kinase induced in liver and muscle by dietary fish oil in fed rats Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E78 - E86. [Abstract] [Full Text] [PDF]

				A. Balbis, G. Baquiran, C. Mounier, and B. I. Posner Effect of Insulin on Caveolin-enriched Membrane Domains in Rat Liver J. Biol. Chem., September 17, 2004; 279(38): 39348 - 39357. [Abstract] [Full Text] [PDF]

				M. Kong, C. Mounier, A. Balbis, G. Baquiran, and B. I. Posner Gab2 Tyrosine Phosphorylation by a Pleckstrin Homology Domain-Independent Mechanism: Role in Epidermal Growth Factor-Induced Mitogenesis Mol. Endocrinol., May 1, 2003; 17(5): 935 - 944. [Abstract] [Full Text] [PDF]

				J. J. Senn, P. J. Klover, I. A. Nowak, and R. A. Mooney Interleukin-6 Induces Cellular Insulin Resistance in Hepatocytes Diabetes, December 1, 2002; 51(12): 3391 - 3399. [Abstract] [Full Text] [PDF]

				J. M. Boylan and P. A. Gruppuso Insulin Receptor Substrate-1 Is Present in Hepatocyte Nuclei from Intact Rats Endocrinology, November 1, 2002; 143(11): 4178 - 4183. [Abstract] [Full Text] [PDF]

				T. Saitoh, T. Yanagita, S. Shiraishi, H. Yokoo, H. Kobayashi, S.-i. Minami, T. Onitsuka, and A. Wada Down-Regulation of Cell Surface Insulin Receptor and Insulin Receptor Substrate-1 Phosphorylation by Inhibitor of 90-kDa Heat-Shock Protein Family: Endoplasmic Reticulum Retention of Monomeric Insulin Receptor Precursor with Calnexin in Adrenal Chromaffin Cells Mol. Pharmacol., October 1, 2002; 62(4): 847 - 855. [Abstract] [Full Text] [PDF]

				F. R. Wettey, S. F. C. Hawkins, A. Stewart, J. P. Luzio, J. C. Howard, and A. P. Jackson Controlled Elimination of Clathrin Heavy-Chain Expression in DT40 Lymphocytes Science, August 30, 2002; 297(5586): 1521 - 1525. [Abstract] [Full Text] [PDF]