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 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 Shooter, G K Articles by Wallace, J C Search for Related Content PubMed PubMed Citation Articles by Shooter, G K Articles by Wallace, J C

Insulin-like growth factor-I (IGF-I) analogues were produced with the aim of identifying IGF-I residues that contribute to the specificity of binding to the type 1 IGF receptor as opposed to the insulin receptor. Receptor binding properties of a series of A- and B-domain analogues were compared using rat L6 myoblasts, soluble human IGF type 1 receptors and soluble human insulin receptor isoforms HIR-A (–Ex11) and HIR-B (+Ex11). IGF-I analogues, [Leu⁸] IGF-I and [Phe⁵⁹] IGF-I, were shown to exhibit respectively, a 28- and 17-fold decrease in affinity for the HIR-A with only a 6- and 5-fold decrease in affinity for the human IGF type 1 receptor. In contrast, the analogue [His⁴] IGF-I was equipotent to IGF-I in binding to the soluble type 1 IGF receptor while showing 7-fold and 4-fold increases in HIR-A and HIR-B binding respectively. Furthermore, [Leu⁶²] IGF-I was 8-fold less potent than IGF-I in soluble IGF type 1 receptor binding but only showed a 2-fold decrease in HIR-A and HIR-B binding. Our study supports the conclusion that the co-evolution of the IGF-I and insulin receptor/ligand systems has resulted in subtle structural differences in the A- and B-regions of each ligand important for defining receptor binding specificity.

This article has been cited by other articles:

				L. Gauguin, C. Delaine, C. L. Alvino, K. A. McNeil, J. C. Wallace, B. E. Forbes, and P. De Meyts Alanine Scanning of a Putative Receptor Binding Surface of Insulin-like Growth Factor-I J. Biol. Chem., July 25, 2008; 283(30): 20821 - 20829. [Abstract] [Full Text] [PDF]

				L. Gauguin, B. Klaproth, W. Sajid, A. S. Andersen, K. A. McNeil, B. E. Forbes, and P. De Meyts Structural Basis for the Lower Affinity of the Insulin-like Growth Factors for the Insulin Receptor J. Biol. Chem., February 1, 2008; 283(5): 2604 - 2613. [Abstract] [Full Text] [PDF]

				C. Delaine, C. L. Alvino, K. A. McNeil, T. D. Mulhern, L. Gauguin, P. De Meyts, E. Y. Jones, J. Brown, J. C. Wallace, and B. E. Forbes A Novel Binding Site for the Human Insulin-like Growth Factor-II (IGF-II)/Mannose 6-Phosphate Receptor on IGF-II J. Biol. Chem., June 29, 2007; 282(26): 18886 - 18894. [Abstract] [Full Text] [PDF]

				A. Denley, C. C. Wang, K. A. McNeil, M. J. E. Walenkamp, H. van Duyvenvoorde, J. M. Wit, J. C. Wallace, R. S. Norton, M. Karperien, and B. E. Forbes Structural and Functional Characteristics of the Val44Met Insulin-Like Growth Factor I Missense Mutation: Correlation with Effects on Growth and Development Mol. Endocrinol., March 1, 2005; 19(3): 711 - 721. [Abstract] [Full Text] [PDF]

				A. Denley, E. R. Bonython, G. W. Booker, L. J. Cosgrove, B. E. Forbes, C. W. Ward, and J. C. Wallace Structural Determinants for High-Affinity Binding of Insulin-Like Growth Factor II to Insulin Receptor (IR)-A, the Exon 11 Minus Isoform of the IR Mol. Endocrinol., October 1, 2004; 18(10): 2502 - 2512. [Abstract] [Full Text] [PDF]