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 04:00:00 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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:10; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DNA
DNA SEQUENCING
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGANDS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RECOMBINANT DNA
STRUCTURAL CHEMICAL ANALYSIS
TRACER TECHNIQUES