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 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 Schumacher, R. Articles by Ullrich, A. Search for Related Content PubMed PubMed Citation Articles by Schumacher, R. Articles by Ullrich, A. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 266, Issue 29, 19288-19295, Oct, 1991

Insulin and insulin-like growth factor-1 binding specificity is determined by distinct regions of their cognate receptors

R Schumacher, L Mosthaf, J Schlessinger, D Brandenburg and A Ullrich
Department of Molecular Biology, Max-Planck-Institut fur Biochemie, Martinsried, Germany.

Chimeric insulin/insulin-like growth factor-1 receptors and insulin receptor alpha-subunit point mutants were characterized with respect to their binding properties for insulin and insulin-like growth factor-1 (IGF-1) and their ability to translate ligand interaction into tyrosine kinase activation in intact cells. We found that replacement of the amino-terminal 137 amino acids of the insulin receptor (IR) with the corresponding 131 amino acids of the IGF-1 receptor (IGF-1R) resulted in loss of affinity for both ligands. Further replacement of the adjacent cysteine region with IGF-1R sequences fully reconstituted affinity for IGF-1, but only marginally for insulin. Unexpectedly, replacement of the IR cysteine-rich domain alone by IGF-1R sequences created a high affinity receptor for both insulin and IGF-1. The binding characteristics of all receptor chimeras reflected the potential of both ligands to regulate the receptor tyrosine kinase activity in intact cells. Our chimeric receptor data, in conjunction with IR amino-terminal domain point mutants, strongly suggest major contributions of structural determinants in both amino- and carboxyl- terminal IR alpha-subunit regions for the formation of the insulin- binding pocket, whereas, surprisingly, the residues defining IGF-1 binding are present predominantly in the cysteine-rich domain of the IGF-1R.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Endocr. Rev., December 1, 2003; 24(6): 737 - 764. [Abstract] [Full Text] [PDF]

				M. Korc Diabetes Mellitus in the Era of Proteomics Mol. Cell. Proteomics, June 1, 2003; 2(6): 399 - 404. [Full Text] [PDF]

				J. Dupont, S. E. Dunn, J. C. Barrett, and D. LeRoith Microarray Analysis and Identification of Novel Molecules Involved in Insulin-like Growth Factor-1 Receptor Signaling and Gene Expression Recent Prog. Horm. Res., January 1, 2003; 58(1): 325 - 342. [Abstract] [Full Text] [PDF]

				J. Whittaker, A. V. Groth, D. C. Mynarcik, L. Pluzek, V. L. Gadsboll, and L. J. Whittaker Alanine Scanning Mutagenesis of a Type 1 Insulin-like Growth Factor Receptor Ligand Binding Site J. Biol. Chem., November 16, 2001; 276(47): 43980 - 43986. [Abstract] [Full Text] [PDF]

				C W Ward, T P J Garrett, N M McKern, M Lou, L J Cosgrove, L G Sparrow, M J Frenkel, P A Hoyne, T C Elleman, T E Adams, et al. The three dimensional structure of the type I insulin-like growth factor receptor Mol. Pathol., June 1, 2001; 54(3): 125 - 132. [Abstract] [Full Text]

				C. Kristensen, F. C. Wiberg, and A. S. Andersen Specificity of Insulin and Insulin-like Growth Factor I Receptors Investigated using Chimeric Mini-Receptors. ROLE OF C-TERMINAL OF RECEPTOR alpha SUBUNIT J. Biol. Chem., December 24, 1999; 274(52): 37351 - 37356. [Abstract] [Full Text] [PDF]

				D. C. Mynarcik, G. Q. Yu, and J. Whittaker Alanine-scanning Mutagenesis of a C-terminal Ligand Binding Domain of the Insulin Receptor alpha Subunit J. Biol. Chem., February 2, 1996; 271(5): 2439 - 2442. [Abstract] [Full Text] [PDF]

				C. Hernández-Sánchez, V. Blakesley, T. Kalebic, L. Helman, and D. LeRoith The Role of the Tyrosine Kinase Domain of the Insulin-like Growth Factor-I Receptor in Intracellular Signaling, Cellular Proliferation, and Tumorigenesis J. Biol. Chem., December 8, 1995; 270(49): 29176 - 29181. [Abstract] [Full Text] [PDF]

				Y. Ruan, C. Chen, Y. Cao, and R. S. Garofalo The Drosophila Insulin Receptor Contains a Novel Carboxyl-terminal Extension Likely to Play an Important Role in Signal Transduction J. Biol. Chem., March 3, 1995; 270(9): 4236 - 4243. [Abstract] [Full Text] [PDF]

				P. F. Williams, D. C. Mynarcik, G. Q. Yu, and J. Whittaker Mapping of an NH(2)-terminal Ligand Binding Site of the Insulin Receptor by Alanine Scanning Mutagenesis J. Biol. Chem., February 17, 1995; 270(7): 3012 - 3016. [Abstract] [Full Text] [PDF]

				R. Liu, J. Zhu, N. Jospe, R. W. Furlanetto, W. Bastian, and J. N. Livingston Deletion of Lysine 121 Creates a Temperature-sensitive Alteration in Insulin Binding by the Insulin Receptor J. Biol. Chem., January 6, 1995; 270(1): 476 - 482. [Abstract] [Full Text] [PDF]