Grunberger G, Zick Y, Gorden P
Science. 1984 Mar 2;223(4639):932-4. doi: 10.1126/science.6141638.
Mononuclear blood cells were obtained from a patient with type A insulin resistance. The cells showed a normal ability to bind iodine 125-labeled insulin. Analysis of solubilized insulin receptors from the patient's cells revealed a defect in insulin-stimulated tyrosine kinase activity, which is closely associated with the receptor itself. The enzyme failed to phosphorylate the insulin receptor and showed a markedly reduced ability to phosphorylate exogenously added substrates. It appears that receptors from this insulin-resistant patient have a defect distal to the insulin-binding site (the alpha subunit of the receptor). The defect could be located in the beta subunit, which has an adenosine triphosphate-binding site, or in another receptor component that transfers a signal of insulin binding into kinase activity. This dissociation between the normal binding and the defective protein kinase component of the insulin receptor represents the first biochemical defect of the receptor distal to ligand binding.
从一名A型胰岛素抵抗患者身上获取了单核血细胞。这些细胞显示出结合125碘标记胰岛素的正常能力。对患者细胞中可溶性胰岛素受体的分析揭示了胰岛素刺激的酪氨酸激酶活性存在缺陷，该活性与受体本身密切相关。该酶无法使胰岛素受体磷酸化，并且对外源添加底物进行磷酸化的能力明显降低。看来，这名胰岛素抵抗患者的受体在胰岛素结合位点（受体的α亚基）远端存在缺陷。该缺陷可能位于具有三磷酸腺苷结合位点的β亚基中，或者位于将胰岛素结合信号转化为激酶活性的另一种受体成分中。胰岛素受体正常结合与缺陷蛋白激酶成分之间的这种分离代表了配体结合远端受体的首个生化缺陷。
