Defects in
insulin receptor function can impair the response of target cells to
insulin. Previously we have described an
insulin resistant patient (leprechaun/Ark-1) with qualitative abnormalities in
insulin binding suggestive of a structural defect in her
insulin receptors. In the present work, we have studied the
tyrosine kinase activity associated with
insulin receptors from cultured Epstein-Barr virus-transformed lymphocytes. In studies of
insulin receptors from leprechaun/Ark-1, we observed that both the magnitude and the dose-dependency of
insulin's effect to stimulate the
tyrosine kinase activity were normal. This suggests that the defect causing this patient's
insulin resistance is independent of the receptor-associated
tyrosine kinase. In the course of these studies, we noted that an anti-receptor antiserum (B-d) had a markedly decreased ability to immunoprecipitate
insulin receptors from leprechaun/Ark-1. This observation further supports our previous conclusion that the
insulin receptor from leprechaun/Ark-1 is abnormal in structure. Moreover, it emphasizes the importance of choosing anti-receptor
antisera which are equally effective at immunoprecipitating receptors from both patients and normal subjects when the anti-receptor
antisera are employed as
reagents in investigations of receptors from
insulin-resistant patients.