The insulin-binding domain of insulin receptor is encoded by exon 2 and exon 3

✍ Scribed by Cecil C. Yip

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 776 KB
• Volume: 48
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240480105

✦ Synopsis

Insulin receptors are disulfide-linked oligotetramers composed of two heterodimers each containing a 130-kDa 01 subunit and a 90-kDa p subunit. Insulin binds to the extracellular 01 subunit, and in the process stimulates the autophosphorylation of the p subunit and the expression of tyrosine kinase activity. Studies combining the use of photoaffinity labeling and immunoprecipitation with anti-peptide antibody have directly demonstrated that the cysteine-rich domain, encoded by exon 3, in the (Y subunit is part of the insulin-binding site of the receptor. Experiments with chimeric insulin receptors and chimeric insulin-like growth factor I receptors have confirmed that the cysteine-rich domain constitutes a part of the insulin-binding site. In addition, results from these experiments suggest that the N-terminal sequence, encoded by exon 2, in the a subunit also participates in insulin binding. In this review it is proposed that, assuming two insulin-binding sites per each holoreceptor oligotetramer, each insulin-binding domain may contain respectively two sub-domains for hydrophobic and charge contact with insulin, and that high-affinity binding would require the interaction of both subunits with the possibility of each subunit reciprocally contributing one of the sub-domains.