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https://hdl.handle.net/2440/28139
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Type: | Journal article |
Title: | Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis - Correlation of binding affinity with ability to prevent apoptosis |
Author: | Forbes, B. Hartfield, P. McNeil, K. Surinya, K. Milner, S. Cosgrove, L. Wallace, J. |
Citation: | The Federation of European Biochemical Societies (FEBS) Journal, 2002; 269(3):961-968 |
Publisher: | Blackwell Science Ltd |
Issue Date: | 2002 |
ISSN: | 1742-464X 0014-2956 |
Statement of Responsibility: | Briony E Forbes, Perry J Hartfield, Kerrie A McNeil, Kathy H Surinya, Steven J Milner, Leah J Cosgrove and John C Wallace |
Abstract: | Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic effects, promotion of differentiation and protection from apoptosis. This study has systematically measured IGF1R binding affinities of IGF-I, IGF-II and 14 IGF analogues to a recombinant high-affinity form of the IGF1R using BIAcore technology. The analogues assessed could be divided into two groups: (a) those designed to investigate binding of IGF-binding protein, which exhibited IGF1R-binding affinities similar to those of IGF-I or IGF-II; (b) those generated to probe IGF1R interactions with greatly reduced IGF1R-binding affinities. The relative binding affinities of IGF-I analogues and IGF-I for the IGF1R determined by BIAcore analysis agreed closely with existing data from receptor-binding assays using cells or tissue membranes, demonstrating that BIAcore technology is a powerful tool for measuring affinities of IGFs for IGF1R. In parallel studies, IGF1R-binding affinities were related to ability to protect against serum withdrawal-induced apoptosis in three different assays including Hoechst 33258 staining, cell survival, and DNA fragmentation assays using the rat pheochromocytoma cell line, PC12. In this model system, IGF-I and IGF-II at low nanomolar concentrations are able to prevent apoptosis completely. We conclude that ability to protect against apoptosis is directly related to ability to bind the IGF1R. |
Description: | European Journal of Biochemistry changed its name to FEBS Journal in January 2005 The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1046/j.0014-2956.2001.02735 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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