This chapter discusses the molecular biology of insulin receptor. Two nearly identical cDNAs containing the human insulin proreceptor have been characterized. These cDNAs encode a 1370- amino-acid or 1382-amino-acid sequence including a 27-residue signal peptide. There are nine single-base discrepancies among the cDNAs, three of which are neutral changes. The major discrepancy between the two clones is a 36-nucleotide insertion, contributing 12 additional amino acids on the C-terminal side of a putative cleavage site separating α- and β-subunits. Mutagenesis of the insulin receptor cDNA has provided strong evidence that the tyrosine kinase encoded within the receptor β-subunit is required for normal receptor function. At least one domain containing autophosphorylation sites is also necessary. The entire cytoplasmic structure is important for signaling specificity as the related tyrosine kinase v-ros will not substitute for the insulin receptor kinase in a hormone-responsive fusion protein. Defined sequences within the cytoplasmic domain of various tyrosine kinases have been suggested as regions that may confer substrate specificity on each enzyme.
|Original language||English (US)|
|Number of pages||16|
|Journal||Progress in Nucleic Acid Research and Molecular Biology|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Molecular Biology