The ligand specificities of the insulin receptor and the insulin-like growth factor I receptor reside in different regions of a common binding site.

To identify the region(s) of the insulin receptor and the insulin-like growth factor I (IGF-I) receptor responsible for ligand specificity (high-affinity binding), expression vectors encoding soluble chimeric insulin/IGF-I receptors were prepared. The chimeric receptors were expressed in mammalian cells and partially purified. Binding studies revealed that a construct comprising an ...
IGF-I receptor in which the 68 N-terminal amino acids of the insulin receptor alpha-subunit had replaced the equivalent IGF-I receptor segment displayed a markedly increased affinity for insulin. In contrast, the corresponding IGF-I receptor sequence is not critical for high-affinity IGF-I binding. It is shown that part of the cysteine-rich domain determines IGF-I specificity. We have previously shown that exchanging exons 1, 2, and 3 of the insulin receptor with the corresponding IGF-I receptor sequence results in loss of high affinity for insulin and gain of high affinity for IGF-I. Consequently, it is suggested that the ligand specificities of the two receptors (i.e., the sequences that discriminate between insulin and IGF-I) reside in different regions of a binding site with common features present in both receptors.
Mesh Terms:
Animals, Binding Sites, Binding, Competitive, Cell Line, Cloning, Molecular, Cricetinae, Exons, Humans, Insulin, Polymerase Chain Reaction, Receptor, Insulin, Receptors, Cell Surface, Receptors, Somatomedin, Recombinant Proteins, Transfection
Proc. Natl. Acad. Sci. U.S.A.
Date: May. 15, 1991
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