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Type: Journal article
Title: Insulin-like growth factor (IGF)- 1 A- and B-domain analogues with altered type 1 IGF and insulin receptor binding specificities
Author: Shooter, G.
Magee, B.
Soos, M.
Francis, G.
Siddle, K.
Wallace, J.
Citation: Journal of Molecular Endocrinology, 1996; 17(3):237-246
Issue Date: 1996
ISSN: 0952-5041
Statement of
Shooter, G K ; Magee, B ; Soos, M A ; Francis, G L ; Siddle, K ; Wallace, J C
Abstract: 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.
RMID: 0030004379
DOI: 10.1677/jme.0.0170237
Appears in Collections:Biochemistry publications

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