MECHANISMS AND ROLES OF PDK1 IN INSULIN SIGNALING

描述：(改编自申请人的摘要) 这项研究的长期目标是阐明分子 胰岛素受体信号转导和生化机制 监管。在这项拟议的研究中，研究人员将重点放在一项新的 鉴定的丝氨酸/苏氨酸激酶，磷酸肌醇依赖蛋白 蛋白激酶1(PDK1)。鉴于一些证据表明，PDK1可能在 胰岛素作用的重要部分、调节机制和确切作用 该酶在信号传递过程中的作用尚不清楚。在建议的 研究，调查者将确定PDK1是否受 磷酸化和寡聚化等机制。调查员将 研究PDK1是否是蛋白激酶N(PKN)的上游激酶 参与胰岛素作用的丝氨酸/苏氨酸蛋白激酶。他 将研究PDK1在胰岛素介导的生物事件中的潜在作用 如糖原合成、葡萄糖转运和蛋白质合成。他会的 检测PDK1是否通过激活在胰岛素信号转导过程中发挥作用 非典型蛋白激酶C亚型和PKN。这些研究的结果 应该提供有关PDK1在生理上的重要性的有用信息 胰岛素信号和增加了我们对胰岛素抵抗的理解，这是一种主要的 II型糖尿病的病因。

DESCRIPTION: (Adapted from the applicant's abstract) The long-term goal of the research is to elucidate the molecular and biochemical mechanisms of insulin receptor signal transduction and regulation. In the proposed study, the investigator is focusing on a newly identified serine/threonine kinase, the phosphoinositide-dependent protein kinase 1 (PDK1). Whereas some evidence suggests that PDK1 may play an important part in insulin action, the regulatory mechanisms and the exact role of the enzyme in the signaling process are still unknown. In the proposed studies, the investigator will determine whether PDK1 is regulated by mechanisms such as phosphorylation and oligomerization. The investigator will investigate whether PDK1 is an upstream kinase for protein kinase N (PKN), a serine/threonine protein kinase that has been implicated in insulin action. He will examine the potential roles of PDK1 in insulin-mediated biological events such as glycogen synthesis, glucose transport and protein synthesis. He will test whether PDK1 exerts its role in insulin signaling processes by activation of atypical protein kinase C isoforms and PKN. Results from these studies should provide useful information on the physiological importance of PDK1 in insulin signaling and add to our understanding of insulin resistance, a primary cause of type II diabetes.