Tyrosine kinase activity of insulin receptors from an insulin-resistant patient with leprechaunism.
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.
D002460:Cell Line; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D010641:Phenotype; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*; D013329:Structure-Activity Relationship
D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin