Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

Journal Article · Tue Aug 14 04:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00484a002· OSTI ID:6102002

Andersen, A S; Kjeldsen, T; Wiberg, F C; Christensen, P M; Rasmussen, J S; Norris, K; Moeller, K B; Moeller, N P.H. ^[1]

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1. Biopharmaceuticals Div., Bagsvaerd (Denmark)

To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the {alpha}-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor.

• OSTI ID: 6102002
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:32; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
DAYS LIVING RADIOISOTOPES
DNA
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
GROWTH FACTORS
HORMONES
INSULIN
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
MEMBRANE PROTEINS
MITOGENS
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
RECOMBINANT DNA
TRACER TECHNIQUES