A thiol-sensitive degradative process of liver uncouples autophosphorylation of the insulin receptor from insulin binding.
A thiol-sensitive degradative process of liver uncouples autophosphorylation of the insulin receptor from insulin binding.
复制标题
肝脏的硫醇敏感降解过程将胰岛素受体的自身磷酸化与胰岛素结合分开。
DOI：
10.1042/bj2360535
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Livingston,JN
中科院分区：
文献类型：
--
作者：
Lerea,KM;Livingston,JN
来自高度纯化的大鼠肝细胞质膜和高尔基体膜的胰岛素受体在胰岛素介导的受体自磷酸化方面表现出差异，尽管它们的胰岛素结合特性相似。这种差异与质膜受体的Mr-90，000 β亚基的Mr-84，000片段的产生有关，该片段在胰岛素结合α亚基没有变化的情况下不存在于高尔基体膜的受体中。当自身磷酸化活性基于胰岛素结合时，质膜衍生的胰岛素受体的活性降低至高尔基体衍生的受体的活性的25-30%。内切糖苷酶F消化产生的MR值为两个物种的变化，但他们没有转化为一个单一的亚基，从而表明在两个亚基的蛋白质组分的差异。虽然蛋白酶抑制剂苯甲磺酰氟，卵类粘蛋白和抑肽酶未能阻止的Mr-84,000片段的形成，碘乙酰胺或EDTA的存在下，在肝匀浆显着抑制片段的产生，并允许质膜胰岛素受体保留自磷酸化活性与高尔基体膜胰岛素受体中存在的。因此，已经鉴定了硫醇敏感的、阳离子依赖的降解活性，其可以将质膜胰岛素受体的胰岛素结合活性与其酪氨酸激酶活性解偶联。
Insulin receptors derived from highly purified rat liver plasma membranes and Golgi membranes showed differences in insulin-mediated receptor autophosphorylation, even though their insulin-binding characteristics were similar. This difference was related to the generation of a Mr-84,000 fragment of the Mr-90,000 beta subunit of the plasma-membrane receptor, a fragment that was not present in the receptor from Golgi membranes, in the absence of a change in the insulin-binding alpha subunit. When autophosphorylation activity was based on insulin binding, the activity of the plasma-membrane-derived insulin receptor was decreased to 25-30% that of the Golgi-derived receptor. Endoglycosidase F digestion produced changes in the Mr values for both species, but they were not converted into a single subunit, thereby suggesting differences in the protein component of the two subunits. Although the proteinase inhibitors phenylmethanesulphonyl fluoride, ovomucoid and aprotinin failed to block the formation of the Mr-84,000 fragment, the presence of iodoacetamide or EDTA during liver homogenization markedly inhibited fragment generation and allowed the plasma-membrane insulin receptor to retain an autophosphorylation activity comparable with that present in insulin receptors from Golgi membranes. Thus a thiol-sensitive, cation-dependent, degrading activity has been identified that can uncouple the insulin-binding activity of the plasma-membrane insulin receptor from its tyrosine kinase activity.