BINDING AFFINITIES OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) FUSION PROTEINS TO IGF BINDING-PROTEIN-1 AND IGF-I RECEPTOR ARE NOT CORRELATED WITH MITOGENIC ACTIVITY

In this report, comparisons between molecular affinities and cellular proliferation activities have been made for insulin-like growth factor -I (IGP-I) and two IGF-I fusion proteins in order to evaluate fusion p roteins as tools for receptor binding studies, Binding affinities and growth promoting effects of the N-terminal fusion Z-IGF-I and the C-te rminal fusion IGF-I-Z, and native recombinant human IGF-I, were analyz ed, Binding kinetic properties of the three IGF-I variants mere analyz ed using BIAcore kinetic interaction analysis testing for binding to b oth human IGF binding protein 1 (IGFBP-1) and a soluble form of the hu man IGF type I receptor extracellular domains (sIGF-I-R), The growth p romoting effects on SaOS-2 human osteosarcoma cells of the different f usion proteins were analyzed, A comparison of receptor binding affinit ies and growth promoting effects shows that the fusion protein recepto r affinity does not correlate with proliferative potential, The IGF-I- Z fusion, with the lowest receptor affinity, shows similar proliferati ve potential to native IGF-I, However, the Z-IGF-I fusion protein, wit h twice the receptor affinity of IGF-I-Z, displays only about 70% of t he IGF-I-Z growth promoting activity, Both IGF-I fusion proteins posse ss similar affinity to IGFBP-1, These results indicate that determinan ts other than the receptor affinity could be involved in the regulatio n of IGF-I proliferative action, This study demonstrates that ligand f usion proteins may be useful to study mechanisms of ligand induced rec eptor activation. (C) 1997 Federation of European Biochemical Societie s.