An investigation of the ligand binding properties and negative cooperatively of soluble insulin-like growth factor receptors
Date
2008
Authors
Surinya, K.
Forbes, B.
Occhiodoro, F.
Booker, G.
Francis, G.
Siddle, K.
Wallace, J.
Cosgrove, L.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Biological Chemistry, 2008; 283(9):5355-5363
Statement of Responsibility
Katharina Helen Surinya, Briony E. Forbes, Filomena Occhiodoro, Grant W. Booker, Geoffrey Leonard Francis, Kenneth Siddle, John C. Wallace, and Leah J. Cosgrove
Conference Name
Abstract
To investigate the interaction of the insulin-like growth factor (IGF) ligands with the insulin-like growth factor type 1 receptor (IGF-1R), we have generated two soluble variants of the IGF-1R. We have recombinantly expressed the ectodomain of IGF-1R or fused this domain to the constant domain from the Fc fragment of mouse immunoglobulin. The ligand binding properties of these soluble IGF-1Rs for IGF-I and IGF-II were investigated using conventional ligand competition assays and BIAcore biosensor technology. In ligand competition assays, the soluble IGF-1Rs both bound IGF-I with similar affinities and a 5-fold lower affinity than that seen for the wild type receptor. In addition, both soluble receptors bound IGF-II with similar affinities to the wild type receptor. BIAcore analyses showed that both soluble IGF-1Rs exhibited similar ligand-specific association and dissociation rates for IGF-I and for IGF-II. The soluble IGF-1R proteins both exhibited negative cooperativity for IGF-I, IGF-II, and the 24-60 antibody, which binds to the IGF-1R cysteine-rich domain. We conclude that the addition of the self-associating Fc domain to the IGF-1R ectodomain does not affect ligand binding affinity, which is in contrast to the soluble ectodomain of the IR. This study highlights some significant differences in ligand binding modes between the IGF-1R and the insulin receptor, which may ultimately contribute to the different biological activities conferred by the two receptors.
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Dissertation Note
Provenance
Description
Originally published online on December 3, 2007
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Rights
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.