Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors

Lauge Schäffer, Thomas Kjeldsen, Asser S. Andersen, Finn C. Wiberg, Ulla D. Larsen, José F. Cara, Raghu Mirmira, Satoe H. Nakagawa, Howard S. Tager

Research output: Contribution to journalArticle

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Abstract

We have examined, by use of a hybrid insulin/insulin-like growth factor-I analog and chimeric insulin/type I insulin-like growth factor receptors, the interplay between ligand and receptor structure in determining the affinity and specificity of hormone-receptor interactions in the insulin and insulin-like growth factor-I systems. Our findings, obtained through the study of radiolabeled peptide binding to detergent-solubilized full-length receptors and to soluble truncated receptors, show that (a) the two-chain hybrid analog exhibits significant cross-reactivity with both receptor systems, (b) the exchange of appropriate domains in chimeric receptors enhances the receptor binding affinity of the analog by 3.5-21-fold, and (c) the affinity of the hybrid analog for the chimeric receptors actually exceeds that of either natural insulin or natural insulin-like growth factor-I. We conclude that the specificity-conferring domains of the insulin and type I insulin-like growth factor receptors reside in different regions of a common binding site, and that the exchange of domains between pairs of related hormones and between pairs of related receptors can yield new ligand-receptor systems with significantly altered affinities and selectivities.

Original languageEnglish (US)
Pages (from-to)3044-3047
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number5
StatePublished - Feb 15 1993
Externally publishedYes

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IGF Type 1 Receptor
Insulin-Like Growth Factor I
Insulin
Hormones
Ligands
Detergents
Binding Sites
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Schäffer, L., Kjeldsen, T., Andersen, A. S., Wiberg, F. C., Larsen, U. D., Cara, J. F., ... Tager, H. S. (1993). Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors. Journal of Biological Chemistry, 268(5), 3044-3047.

Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors. / Schäffer, Lauge; Kjeldsen, Thomas; Andersen, Asser S.; Wiberg, Finn C.; Larsen, Ulla D.; Cara, José F.; Mirmira, Raghu; Nakagawa, Satoe H.; Tager, Howard S.

In: Journal of Biological Chemistry, Vol. 268, No. 5, 15.02.1993, p. 3044-3047.

Research output: Contribution to journalArticle

Schäffer, L, Kjeldsen, T, Andersen, AS, Wiberg, FC, Larsen, UD, Cara, JF, Mirmira, R, Nakagawa, SH & Tager, HS 1993, 'Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors', Journal of Biological Chemistry, vol. 268, no. 5, pp. 3044-3047.
Schäffer, Lauge ; Kjeldsen, Thomas ; Andersen, Asser S. ; Wiberg, Finn C. ; Larsen, Ulla D. ; Cara, José F. ; Mirmira, Raghu ; Nakagawa, Satoe H. ; Tager, Howard S. / Interactions of a hybrid insulin/insulin-like growth factor-I analog with chimeric insulin/type I insulin-like growth factor receptors. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 5. pp. 3044-3047.
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