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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
Author(s) -
Jansson Magnus,
Dixelius Johan,
Uhlen Mathias,
Nilsson Björn O
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01149-6
Subject(s) - fusion protein , receptor , affinities , insulin like growth factor 2 receptor , growth factor , insulin like growth factor , insulin like growth factor binding protein , ligand (biochemistry) , biology , chemistry , biochemistry , recombinant dna , insulin like growth factor 1 receptor , gene
In this report, comparisons between molecular affinities and cellular proliferation activities have been made for insulin‐like growth factor‐I (IGF‐I) and two IGF‐I fusion proteins in order to evaluate fusion proteins as tools for receptor binding studies. Binding affinities and growth promoting effects of the N‐terminal fusion Z‐IGF‐I and the C‐terminal fusion IGF‐I‐Z, and native recombinant human IGF‐I, were analyzed. Binding kinetic properties of the three IGF‐I variants were analyzed using BIAcore kinetic interaction analysis testing for binding to both human IGF binding protein 1 (IGFBP‐1) and a soluble form of the human IGF type I receptor extracellular domains (sIGF‐I R ). The growth promoting effects on SaOS‐2 human osteosarcoma cells of the different fusion proteins were analyzed. A comparison of receptor binding affinities and growth promoting effects shows that the fusion protein receptor affinity does not correlate with proliferative potential. The IGF‐I‐Z fusion, with the lowest receptor affinity, shows similar proliferative potential to native IGF‐I. However, the Z‐IGF‐I fusion protein, with twice the receptor affinity of IGF‐I‐Z, displays only about 70% of the IGF‐I‐Z growth promoting activity. Both IGF‐I fusion proteins possess similar affinity to IGFBP‐1. These results indicate that determinants other than the receptor affinity could be involved in the regulation of IGF‐I proliferative action. This study demonstrates that ligand fusion proteins may be useful to study mechanisms of ligand induced receptor activation.