The Institute for Adult Disease, Asahi Life Foundation.
Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(10):581-589. doi: 10.2183/pjab.95.039.
Immunoprecipitation with autoantibodies to the insulin receptor derived from patients with extreme insulin resistance and acanthosis nigricans revealed that the receptor is comprised of two subunits of 135 kDa (α subunit) and 95 kDa (β subunit) and that insulin induces the rapid phosphorylation of the β subunit in intact cells. Incubation of a highly purified insulin receptor preparation with [γ-P]ATP also resulted in tyrosine phosphorylation of the β subunit in an insulin-dependent manner, suggesting that the receptor itself is a tyrosine-specific protein kinase. Furthermore, a Japanese boy with insulin resistance and acanthosis nigricans was found to be heterozygous for a mutation of the insulin receptor gene that resulted in the replacement of glycine-996 with valine in the ATP binding site of the receptor. Expression of the mutant receptor in cultured cells revealed it to be deficient in tyrosine kinase activity and mediation of insulin action, suggesting that the tyrosine kinase activity of the insulin receptor is essential for insulin action in vivo.
用来自严重胰岛素抵抗伴黑棘皮病患者的自身抗体进行免疫沉淀显示，胰岛素受体由两个亚基组成，分子量分别为 135 kDa（α 亚基）和 95 kDa（β 亚基），胰岛素能在完整细胞中诱导β亚基的快速磷酸化。用[γ-P]ATP 孵育高度纯化的胰岛素受体制剂也能以胰岛素依赖的方式使β亚基发生酪氨酸磷酸化，提示受体本身就是一种酪氨酸特异性蛋白激酶。此外，还发现一名患有胰岛素抵抗伴黑棘皮病的日本男孩，其胰岛素受体基因发生杂合突变，导致受体 ATP 结合部位的甘氨酸 996 被缬氨酸取代。在培养细胞中表达突变受体表明，其酪氨酸激酶活性和胰岛素作用的介导均有缺陷，提示胰岛素受体的酪氨酸激酶活性对体内胰岛素作用是必需的。
