INTERACTION BETWEEN THE INSULIN RECEPTOR AND TRAP

胰岛素受体和陷阱之间的相互作用

• 批准号: 6431483
• 负责人: MICHEL BERNIER
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431483
• 关键词: CHO cells; biocytin; biotin; hydrogen peroxide; immunoprecipitation; insulin receptor; oxidative stress; oxidoreductase inhibitor; protein structure function; sulfhydryl reagents; thiols; vanadium

Summary of work: A number of signaling intermediates and membrane-associated glycoproteins can regulate the insulin receptor function by interacting with different regions of this receptor. Because of the important role that intracellular reduction/oxidation potential plays in the modulation of insulin action, we postulated that the interaction between the insulin receptor and associated proteins may be affected by the reactivity of the receptor cytoplasmic thiol(s). In this study, we examined the role of various receptor domains and specific insulin receptor cysteine residues in this association. The results showed the formation of a large complex between the wild-type human insulin receptor beta-subunit and TRAP, a thiol reactive membrane-associated protein, whose identity remains to be elucidated. A series of experiments revealed that a single cysteine residue near the juxtamembrane region of the human insulin receptor is responsible for this interaction. Known signaling intermediates are not part of the receptor-TRAP complex. Hence, work is underway to identify TRAP. Also, the effects of oxidants and antioxidants on the formation and cellular distribution of the insulin receptor-TRAP heterocomplex is currently evaluated. Since TRAP is associated with the insulin receptor cytoplasmic domain both in unstimulated cells and cells treated with insulin, it may represent an accessory protein that interacts constitutively with the insulin receptor, enabling recruitment of signaling intermediates at the plasma membrane in response to insulin challenge.

工作概述：许多信号中间体和膜相关糖蛋白通过与胰岛素受体不同区域的相互作用来调节胰岛素受体的功能。由于细胞内还原/氧化电位在胰岛素作用的调节中起重要作用，我们假设胰岛素受体和相关蛋白之间的相互作用可能受到受体细胞质硫醇的反应性的影响。在这项研究中，我们研究了各种受体结构域和特定胰岛素受体半胱氨酸残基在这种关联中的作用。结果显示，野生型人胰岛素受体β -亚基与巯基反应性膜相关蛋白TRAP之间形成了一个大的复合物，其身份仍有待阐明。一系列的实验表明，人类胰岛素受体近膜区域附近的一个半胱氨酸残基是这种相互作用的原因。已知的信号中间体不是受体- trap复合物的一部分。因此，确定陷阱的工作正在进行中。此外，氧化剂和抗氧化剂对胰岛素受体- trap异复合体的形成和细胞分布的影响目前正在评估中。由于TRAP在未受胰岛素刺激的细胞和经胰岛素处理的细胞中都与胰岛素受体细胞质域相关，因此它可能代表一种辅助蛋白，与胰岛素受体组成性地相互作用，使信号中间体在响应胰岛素挑战时能够在质膜上募集。