Functional Analysis of the Beta-Cell

Beta 细胞的功能分析

• 批准号: 6923625
• 负责人: Roger J Davis
• 金额: $ 47.06万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6923625
• 关键词: JUN kinase; antiserum; biological signal transduction; blood glucose; diabetes mellitus; diabetes mellitus genetics; disease /disorder model; enzyme activity; enzyme mechanism; gene mutation; gene targeting; genetic models; glucose tolerance test; histology; immunologic substance development /preparation; insulin; laboratory mouse; laboratory rabbit; mitogen activated protein kinase; pancreatic islets; protein protein interaction; protein structure function

DESCRIPTION (provided by applicant): The overall goal of this research program is to understand the role of the c-Jun N-terminal kinase (JNK) group of mitogen-activated protein (MAP) kinases. Many of the components of the JNK protein kinase cascade have been identified by molecular cloning and have been characterized in biochemical studies. However, an understanding of the physiological role of the JNK signaling pathway has remained elusive. The long-term goal of this research is to define function of the JNK signaling pathway in the beta cell. Previous studies have demonstrated that JNK can phosphorylate and inhibit the function of insulin receptor substrate (IRS) proteins. In addition, the JIP scaffold proteins that co-ordinate the JNK protein kinase cascade have been found to be mutated in diabetic humans. We have constructed several mouse models with defects in the JNK signaling pathway, including mice with defects in the JIP scaffold proteins. These mouse models will be used to study the function of these proteins in beta cells Achievement of the goals of this proposal will increase understanding of signal transduction; mechanisms that contribute to normal beta cell function. This information may represent a basis for the design of novel therapeutic strategies for the treatment of diabetes. The Specific Aims of this proposal are to employ mouse models to: Define the role of JNK in beta cells. Define the role of JIP scaffold proteins in beta cells Define the function of diabetes-associated mutations in JIP1

描述（由申请人提供）： 该研究计划的总体目标是了解丝裂原激活蛋白 (MAP) 激酶的 c-Jun N 末端激酶 (JNK) 组的作用。 JNK 蛋白激酶级联的许多成分已通过分子克隆得到鉴定，并在生化研究中得到表征。然而，对 JNK 信号通路的生理作用的了解仍然难以捉摸。这项研究的长期目标是确定 β 细胞中 JNK 信号通路的功能。 先前的研究表明，JNK 可以磷酸化并抑制胰岛素受体底物 (IRS) 蛋白的功能。此外，协调 JNK 蛋白激酶级联的 JIP 支架蛋白被发现在糖尿病人体内发生突变。我们构建了几种JNK信号通路缺陷的小鼠模型，其中包括JIP支架蛋白缺陷的小鼠。这些小鼠模型将用于研究这些蛋白质在β细胞中的功能 该提案目标的实现将增加对信号转导的理解；有助于正常 β 细胞功能的机制。该信息可能代表设计治疗糖尿病的新治疗策略的基础。 该提案的具体目标是利用小鼠模型来： 定义 JNK 在 β 细胞中的作用。 定义 JIP 支架蛋白在 β 细胞中的作用 定义 JIP1 中糖尿病相关突变的功能