Leu 193 mutation in the cysteine rich region of the insulin receptor inhibits the cleavage of the insulin receptor precursor but not insulin binding.

To characterize the Leu 193 mutant insulin receptor, which was found in a patient with extreme insulin resistance, the mutant insulin receptor was overexpressed in Rat-1 fibroblasts by transfection of mutated insulin receptor cDNA. In the pulse-chase experiment, the cleavage of the proreceptors to the matured receptor subunits was impaired in the cells expressing Leu 193 insulin receptor and therefore, the mutant proreceptors were accumulated in the cell. Insulin bound to the Leu 193 insulin receptor on the cell surface with normal affinity, although the mutation was in the alpha-subunit of the insulin receptor. Therefore, the Leu 193 mutation impaired proreceptor cleavage but not insulin binding.