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. 1991 May 15;88(10):4404–4408. doi: 10.1073/pnas.88.10.4404

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

T Kjeldsen 1, A S Andersen 1, F C Wiberg 1, J S Rasmussen 1, L Schäffer 1, P Balschmidt 1, K B Møller 1, N P Møller 1
PMCID: PMC51668  PMID: 1852007

Abstract

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.

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Selected References

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