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MECHANISMS AND ROLES OF PDK1 IN INSULIN SIGNALING

PDK1 在胰岛素信号传导中的机制和作用

基本信息

批准号：
6761636
负责人：
FENG LIU
金额：
$ 3.53万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6761636
关键词：
active sites biological signal transduction enzyme activity enzyme mechanism glucose metabolism glycogenesis hormone regulation /control mechanism insulin isozymes phosphatidylinositol 3 kinase protein kinase protein kinase C tissue /cell culture yeast two hybrid system

项目摘要

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.

描述：（改编自申请人摘要）这项研究的长期目标是阐明和胰岛素受体信号转导的生化机制，调控在拟议的研究中，研究人员正在关注一种新的鉴定的丝氨酸/苏氨酸激酶，磷酸肌醇依赖性蛋白激酶1（PDK 1）。尽管有证据表明PDK 1可能在胰岛素作用的重要部分，调节机制和确切作用这种酶在信号传导过程中的作用仍然未知。拟议研究者将确定PDK 1是否受以下因素的调节：例如磷酸化和寡聚化的机制。研究者将研究PDK 1是否是蛋白激酶N（PKN）的上游激酶，丝氨酸/苏氨酸蛋白激酶，其与胰岛素作用有关。他将研究PDK 1在胰岛素介导的生物学事件中的潜在作用如糖原合成、葡萄糖转运和蛋白质合成。他将测试PDK 1是否通过激活在胰岛素信号传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用的信息，PDK 1的生理重要性，胰岛素信号转导和增加我们对胰岛素抵抗的理解， 2型糖尿病的病因