TAILIEUCHUNG - Báo cáo Y học: Characteristics of binding of insulin-like growth factor (IGF)-I and IGF-II analogues to the type 1 IGF receptor determined by BIAcore analysis

Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic e ects, promotion of di erentiation and protection from apoptosis. This study has systematically measured IGF1R binding a nities of IGF-I, IGF-II and 14 IGF analogues to a recombinant high-a nity 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 a nities similar to those of IGF-I or IGF-II;. | Eur. J. Biochem. 269 961-968 2002 FEBS 2002 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 Rrionv F_ Forbes1 . Perrv J. Hartfield2 . Kerrie A. McNeil1. Kathv H_ Surinva1 . Steven J Milner3. Ul lull y kalVIMC Idly Ja liaitllviu f l vl I I c a ITIVI1CII f IVll HI y Ila JUI Illy u If ldrdl Ji Iflllllvl f Leah Ja Cosgrove4 and John Ca Wallace1 1Department of Molecular Biosciences Adelaide University SA Australia 2School of Biomedical Sciences Faculty of Medical and Health Sciences University of Newcastle Callaghan NSW Australia GroPep Ltd Thebarton SA Australia 4CSIRO Health Sciences and Nutrition Adelaide SA Australia 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 .

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