Endocrinology, Vol 136, 431-439, Copyright © 1995 by Endocrine Society

ARTICLES

Epidermal growth factor (EGF) receptor carboxy-terminal domains are required for EGF-induced glucose transport in transgenic 3T3-L1 adipocytes

RW Hardy, KB Gupta, JM McDonald, J Williford and A Wells
Department of Pathology, University of Alabama at Birmingham 35294.

Insulin-stimulated glucose transport in adipocytes is mediated by the insulin receptor. To ascertain whether a related receptor could also trigger this response, the epidermal growth factor (EGF) receptor (EGFR) was introduced into adipocytes. 3T3-L1 fibroblasts were infected by a retroviral construct encoding either the full-length (WT) or a carboxy-terminal truncated (c'973) human EGFR; truncation of the amino acids distal to 973 removes all autophosphorylation motifs. After selection and conversion to adipocytes, the level of EGFR expression was retained in infectant adipocytes (150,000 and 250,000/cell, respectively), but not in the parental 3T3-L1 adipocytes (< 5000/cell). WT and c'973 EGFR exhibited ligand-dependent tyrosine kinase activity and stimulated mitogen-activated protein kinase activity equivalently; neither phosphorylated insulin receptor substrate-1. WT EGFR, but not c'973 EGFR, underwent ligand-induced autophosphorylation. EGF did not stimulate tyrosine phosphorylation of the insulin receptor or insulin receptor substrate-1. EGF had a minimal effect on glucose transport by parental 3T3-L1 adipocytes. Glucose transport in the WT EGFR adipocytes was stimulated equivalently by insulin and EGF; exposure to insulin and EGF in combination did not result in augmented transport. Glucose transport in the c'973 EGFR adipocytes was stimulated by insulin, but not by EGF. GLUT4 was translocated to the plasma membrane to a similar extent in response to insulin or EGF in the WT EGFR adipocytes; only insulin caused a significant GLUT4 translocation in the parental or c'973 EGFR adipocytes. These data suggest that the insulin and EGF signaling pathways that lead to glucose transport converge in these adipocytes down-stream of the insulin receptor, and that activation of this pathway requires signaling motifs in the carboxy-terminus of the EGFR. This model system represents a novel approach with which to dissect signal transduction pathways in terminally differentiated adipocytes.

This article has been cited by other articles:

				M. Y. Lee, S. H. Park, Y. J. Lee, J. S. Heo, J. H. Lee, and H. J. Han EGF-induced inhibition of glucose transport is mediated by PKC and MAPK signal pathways in primary cultured chicken hepatocytes Am J Physiol Gastrointest Liver Physiol, October 1, 2006; 291(4): G744 - G750. [Abstract] [Full Text] [PDF]

				T. Yuasa, R. Kakuhata, K. Kishi, T. Obata, Y. Shinohara, Y. Bando, K. Izumi, F. Kajiura, M. Matsumoto, and Y. Ebina Platelet-Derived Growth Factor Stimulates Glucose Transport in Skeletal Muscles of Transgenic Mice Specifically Expressing Platelet-Derived Growth Factor Receptor in the Muscle, but It Does Not Affect Blood Glucose Levels Diabetes, November 1, 2004; 53(11): 2776 - 2786. [Abstract] [Full Text] [PDF]

				E. L. Whiteman, J. J. Chen, and M. J. Birnbaum Platelet-Derived Growth Factor (PDGF) Stimulates Glucose Transport in 3T3-L1 Adipocytes Overexpressing PDGF Receptor by a Pathway Independent of Insulin Receptor Substrates Endocrinology, September 1, 2003; 144(9): 3811 - 3820. [Abstract] [Full Text] [PDF]

				S. Gogg and U. Smith Epidermal Growth Factor and Transforming Growth Factor alpha Mimic the Effects of Insulin in Human Fat Cells and Augment Downstream Signaling in Insulin Resistance J. Biol. Chem., September 20, 2002; 277(39): 36045 - 36051. [Abstract] [Full Text] [PDF]

				L. Wang, H. Hayashi, and Y. Ebina Transient Effect of Platelet-derived Growth Factor on GLUT4 Translocation in 3T3-L1 Adipocytes J. Biol. Chem., July 2, 1999; 274(27): 19246 - 19253. [Abstract] [Full Text] [PDF]

				A. G. Kayali, J. Eichhorn, T. Haruta, A. J. Morris, J. G. Nelson, P. Vollenweider, J. M. Olefsky, and N. J. G. Webster Association of the Insulin Receptor with Phospholipase C-gamma (PLCgamma ) in 3T3-L1 Adipocytes Suggests a Role for PLCgamma in Metabolic Signaling by Insulin J. Biol. Chem., May 29, 1998; 273(22): 13808 - 13818. [Abstract] [Full Text] [PDF]

				V. R. Fantin, J. D. Sparling, J. W. Slot, S. R. Keller, G. E. Lienhard, and B. E. Lavan Characterization of Insulin Receptor Substrate 4 in Human Embryonic Kidney 293 Cells J. Biol. Chem., April 24, 1998; 273(17): 10726 - 10732. [Abstract] [Full Text] [PDF]

				M. Van Epps-Fung, K. Gupta, R. W. Hardy, and A. Wells A Role for Phospholipase C Activity in GLUT4-Mediated Glucose Transport Endocrinology, December 1, 1997; 138(12): 5170 - 5175. [Abstract] [Full Text] [PDF]

				M. Van Epps-Fung, J. Williford, A. Wells, and R. W. Hardy Fatty Acid-Induced Insulin Resistance in Adipocytes Endocrinology, October 1, 1997; 138(10): 4338 - 4345. [Abstract] [Full Text] [PDF]

				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]