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

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miele, C. Articles by Beguinot, F. Search for Related Content PubMed PubMed Citation Articles by Miele, C. Articles by Beguinot, F. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 5, 3094-3102, January 29, 1999

Differential Role of Insulin Receptor Substrate (IRS)-1 and IRS-2 in L6 Skeletal Muscle Cells Expressing the Arg¹¹⁵²  Gln Insulin Receptor

Claudia Miele, Matilde Caruso, Veronique Calleja^¶, Renata Auricchio, Francesco Oriente, Pietro Formisano, Gerolama Condorelli, Almerinda Cafieri, Dominique Sawka-Verhelle^¶, Emmanuel Van Obberghen^¶, and Francesco Beguinot

From the  Dipartimento di Biologia e Patologia Cellulare e Molecolare & Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Federico II University of Naples, 80131 Naples, Italy and ^¶ INSERM U145, 06107 Nice Cedex 2, France

In L6 muscle cells expressing the Arg¹¹⁵²  Gln insulin receptor (Mut), basal tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was increased by 35% compared with wild-type cells (WT). Upon exposure to insulin, IRS-1 phosphorylation increased by 12-fold in both the Mut and WT cells. IRS-2 was constitutively phosphorylated in Mut cells and not further phosphorylated by insulin. The maximal phosphorylation of IRS-2 in basal Mut cells was paralleled by a 4-fold increased binding of the kinase regulatory loop binding domain of IRS-2 to the Arg¹¹⁵²  Gln receptor. Grb2 and phosphatidylinositol 3-kinase association to IRS-1 and IRS-2 reflected the phosphorylation levels of the two IRSs. Mitogen-activated protein kinase activation and [³H]thymidine incorporation closely correlated with IRS-1 phosphorylation in Mut and WT cells, while glycogen synthesis and synthase activity correlated with IRS-2 phosphorylation. The Arg¹¹⁵²  Gln mutant did not signal Shc phosphorylation or Shc-Grb2 association in intact L6 cells, while binding Shc in a yeast two-hybrid system and phosphorylating Shc in vitro. Thus, IRS-2 appears to mediate insulin regulation of glucose storage in Mut cells, while insulin-stimulated mitogenesis correlates with the activation of the IRS-1/mitogen-activated protein kinase pathway in these cells. IRS-1 and Shc-mediated mitogenesis may be redundant in muscle cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Perrini, A. Natalicchio, L. Laviola, A. Cignarelli, M. Melchiorre, F. De Stefano, C. Caccioppoli, A. Leonardini, S. Martemucci, G. Belsanti, et al. Abnormalities of Insulin-Like Growth Factor-I Signaling and Impaired Cell Proliferation in Osteoblasts from Subjects with Osteoporosis Endocrinology, March 1, 2008; 149(3): 1302 - 1313. [Abstract] [Full Text] [PDF]

				C. Huang, A. C. P. Thirone, X. Huang, and A. Klip Differential Contribution of Insulin Receptor Substrates 1 Versus 2 to Insulin Signaling and Glucose Uptake in L6 Myotubes J. Biol. Chem., May 13, 2005; 280(19): 19426 - 19435. [Abstract] [Full Text] [PDF]

				L. Laviola, S. Perrini, G. Belsanti, A. Natalicchio, C. Montrone, A. Leonardini, A. Vimercati, M. Scioscia, L. Selvaggi, R. Giorgino, et al. Intrauterine Growth Restriction in Humans Is Associated with Abnormalities in Placental Insulin-Like Growth Factor Signaling Endocrinology, March 1, 2005; 146(3): 1498 - 1505. [Abstract] [Full Text] [PDF]

				F. Fiory, F. Oriente, C. Miele, C. Romano, A. Trencia, A. T. Alberobello, I. Esposito, R. Valentino, F. Beguinot, and P. Formisano Protein Kinase C-{zeta} and Protein Kinase B Regulate Distinct Steps of Insulin Endocytosis and Intracellular Sorting J. Biol. Chem., March 19, 2004; 279(12): 11137 - 11145. [Abstract] [Full Text] [PDF]

				I. Rakatzi, S. Ramrath, D. Ledwig, O. Dransfeld, T. Bartels, G. Seipke, and J. Eckel A Novel Insulin Analog With Unique Properties: LysB3,GluB29 Insulin Induces Prominent Activation of Insulin Receptor Substrate 2, but Marginal Phosphorylation of Insulin Receptor Substrate 1 Diabetes, September 1, 2003; 52(9): 2227 - 2238. [Abstract] [Full Text] [PDF]

				G. Bifulco, C. Di Carlo, M. Caruso, F. Oriente, A. Di Spiezio Sardo, P. Formisano, F. Beguinot, and C. Nappi Glucose Regulates Insulin Mitogenic Effect by Modulating SHP-2 Activation and Localization in JAr Cells J. Biol. Chem., June 28, 2002; 277(27): 24306 - 24314. [Abstract] [Full Text] [PDF]

				L. Laviola, G. Belsanti, A. M. Davalli, R. Napoli, S. Perrini, G. C. Weir, R. Giorgino, and F. Giorgino Effects of Streptozocin Diabetes and Diabetes Treatment by Islet Transplantation on In Vivo Insulin Signaling in Rat Heart Diabetes, December 1, 2001; 50(12): 2709 - 2720. [Abstract] [Full Text] [PDF]

				G. Condorelli, G. Vigliotta, A. Trencia, M. A. Maitan, M. Caruso, C. Miele, F. Oriente, S. Santopietro, P. Formisano, and F. Beguinot Protein Kinase C (PKC)-{alpha} Activation Inhibits PKC-{zeta} and Mediates the Action of PED/PEA-15 on Glucose Transport in the L6 Skeletal Muscle Cells Diabetes, June 1, 2001; 50(6): 1244 - 1252. [Abstract] [Full Text]

				G. D. Wadley, R. J. Tunstall, A. Sanigorski, G. R. Collier, M. Hargreaves, and D. Cameron-Smith Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle J Appl Physiol, February 1, 2001; 90(2): 436 - 440. [Abstract] [Full Text] [PDF]

				P. Formisano, F. Oriente, F. Fiory, M. Caruso, C. Miele, M. A. Maitan, F. Andreozzi, G. Vigliotta, G. Condorelli, and F. Beguinot Insulin-Activated Protein Kinase Cbeta Bypasses Ras and Stimulates Mitogen-Activated Protein Kinase Activity and Cell Proliferation in Muscle Cells Mol. Cell. Biol., September 1, 2000; 20(17): 6323 - 6333. [Abstract] [Full Text]

				A. V. Chibalin, M. Yu, J. W. Ryder, X. M. Song, D. Galuska, A. Krook, H. Wallberg-Henriksson, and J. R. Zierath Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2 PNAS, January 4, 2000; 97(1): 38 - 43. [Abstract] [Full Text] [PDF]

				M. Caruso, C. Miele, F. Oriente, A. Maitan, G. Bifulco, F. Andreozzi, G. Condorelli, P. Formisano, and F. Beguinot In L6 Skeletal Muscle Cells, Glucose Induces Cytosolic Translocation of Protein Kinase C-alpha and Trans-activates the Insulin Receptor Kinase J. Biol. Chem., October 1, 1999; 274(40): 28637 - 28644. [Abstract] [Full Text] [PDF]

				P. Lebrun, V. Baron, C. R. Hauck, D. D. Schlaepfer, and E. Van Obberghen Cell Adhesion and Focal Adhesion Kinase Regulate Insulin Receptor Substrate-1 Expression J. Biol. Chem., December 1, 2000; 275(49): 38371 - 38377. [Abstract] [Full Text] [PDF]

				F. Oriente, P. Formisano, C. Miele, F. Fiory, M. A. Maitan, G. Vigliotta, A. Trencia, S. Santopietro, M. Caruso, E. Van Obberghen, et al. Insulin Receptor Substrate-2 Phosphorylation Is Necessary for Protein Kinase Czeta Activation by Insulin in L6hIR Cells J. Biol. Chem., September 28, 2001; 276(40): 37109 - 37119. [Abstract] [Full Text] [PDF]

				M. Caruso, M. A. Maitan, G. Bifulco, C. Miele, G. Vigliotta, F. Oriente, P. Formisano, and F. Beguinot Activation and Mitochondrial Translocation of Protein Kinase Cdelta Are Necessary for Insulin Stimulation of Pyruvate Dehydrogenase Complex Activity in Muscle and Liver Cells J. Biol. Chem., November 21, 2001; 276(48): 45088 - 45097. [Abstract] [Full Text] [PDF]