The rat insulin receptor: primary structure and conservation of tissue-specific alternative messenger RNA splicing.

To investigate whether alterations in the polypeptide structure of the insulin receptor might explain the heterogeneity observed in its properties between species and in different tissues, we obtained the complete primary structure of the rat liver insulin receptor precursor by cDNA cloning and sequencing. The rat proreceptor contains 1357 amino acids and has 95.2% identity with deduced polypeptide sequences reported for the human insulin receptor precursor. In addition, the rat liver insulin receptor cDNA was similar to the form of the human insulin receptor mRNA that contains Exon 11 in its coding region, which undergoes tissue-specific alternative splicing. Using the polymerase chain reaction to amplify a cDNA segment corresponding to this region in several rat tissues, the splicing pattern of sequences homologous to Exon 11 was found to be highly conserved, providing further evidence that these two forms of the insulin receptor may serve important functional or regulatory roles. These studies have also identified subtle variations in the primary structure of the insulin receptor which may influence its properties between species.