Prozorovskiĭ V N, Lokhov P G, Maslov D L, Ipatova O M
Institute of Biomedical Chemistry, RAMS, Russia, 119121, Pogodinskaya Street, 10, Moscow.
Biomed Khim. 2003 Jan-Feb;49(1):46-62.
On the basis of analysis of own and literature data on insulin-receptor interaction two centers responsible for receptor binding were identified on 3D-structure of insulin with receptor. Two extracellular domains of insulin receptor interact with these centers on insulin molecule. The comparative analysis of primary structures of the protein disulfide isomerase thioredoxine domains and C-terminal domain of the receptor suggests existence of the thioredoxine domain in the insulin receptor. In this connection the role of the thiol disulfide an exchange reaction is discussed in terms of insulin interaction with receptor followed by subsequent conformational changes in the receptor molecule and activation of the intercellular tyrosine kinase domain. It is supposed, that besides known mechanism of receptor mediated insulin signal transduction and tyrosine kinase activation, there is other mechanism of insulin intracellular signal transduction realised via cytosolic insulin-binding proteins. Major components of intercellular insulin signal transduction include: protein disulfide isomerase and insulin degrading enzyme. The importance of change of the intracellular insulin degradation rate for insulin signal transduction is discussed.
基于对自身及文献中胰岛素与受体相互作用数据的分析，在胰岛素与受体的三维结构上确定了两个负责受体结合的位点。胰岛素受体的两个细胞外结构域与胰岛素分子上的这些位点相互作用。对蛋白质二硫键异构酶硫氧还蛋白结构域和受体C末端结构域一级结构的比较分析表明，胰岛素受体中存在硫氧还蛋白结构域。就此，从胰岛素与受体相互作用以及随后受体分子的构象变化和细胞内酪氨酸激酶结构域的激活方面，讨论了硫醇 - 二硫键交换反应的作用。据推测，除了已知的受体介导的胰岛素信号转导和酪氨酸激酶激活机制外，还存在通过胞质胰岛素结合蛋白实现的胰岛素细胞内信号转导的其他机制。细胞间胰岛素信号转导的主要成分包括：蛋白质二硫键异构酶和胰岛素降解酶。讨论了细胞内胰岛素降解速率变化对胰岛素信号转导的重要性。
