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

Journal Article · Wed May 15 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.10.4404· OSTI ID:5933970

Kjeldsen, T; Andersen, A S; Wiberg, F C; Rasmussen, J S; Schaeffer, L; Balschmidt, P; Moller, K B; Moller, N P.H. ^[1]

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1. Novo Nordisk, Bagsvaerd (Denmark)

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. The authors 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.

• OSTI ID: 5933970
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:10; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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