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Contribution of the Residue Glu9, Glu46, and Phe49 to the Biological Activity of Insulin‐Like Growth Factor‐1
Author(s) -
Chen Hui,
Feng YouMin
Publication year - 2001
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540118769
Subject(s) - residue (chemistry) , insulin , mutant , chemistry , biological activity , insulin like growth factor , in vitro , recombinant dna , growth factor , biochemistry , biology , endocrinology , receptor , gene
Abstract Three recombinant single‐chain insulin mutants, [B10Glu]Ins/IGF‐1(C), [A5Glu]PIP, and [A8Tyr]PIP were prepared by means of protein engineering. In the three mutants, the residue at position 10 of insulin B chain and positions 5 and 8 of insulin A chain were substituted by the corresponding residue Glu9, Glu46, and an aromatic residue at 49 of IGF‐1, respectively. The growth‐promoting activity of [B18Glu]Ins/IGF‐1(C) is 58‐fold higher than insulin and of [A5Glu]PIP, and [A8Tyr]PIP is 2.5‐ and 4.7‐fold higher than PIP, respectively, measured using a mouse mammary tumor cell line GR2H6 in vitro. The results show that the residues Glu9, Glu46, and Phe49, especially the Glu9, play an important role in the growth‐promoting function of IGF‐1. Based on the results, we suggest that the insulin could be used as a scaffold to investigate the contributions of residues of IGF‐1 to its biological function.