The Regulation of Glucose Transport by Insulin

胰岛素对葡萄糖转运的调节

• 批准号: 6445826
• 负责人: JOSEPH B HWANG
• 金额: $ 4.42万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-12 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6445826
• 关键词: binding sites; cell line; cell membrane; clone cells; glucose transport; glucose transporter; hormone regulation /control mechanism; insulin; mutant; protein structure function; restriction fragment length polymorphism; yeast two hybrid system

DESCRIPTION: (Provided By Applicant) Insulin stimulates glucose uptake into muscle and adipose tissue through the translocation of the insulin-responsive glucose transporter type 4 (GLUT4) from an intracellular compartment to the cell surface. Although this translocation event requires the activation of phosphatidylinositol 3-kinase (PI 3-kinase) it is not sufficient, implicating a second signaling pathway. The PI 3-kinase-independent pathway involves the tyrosinc phosphorylation of the proto-oncogene c-cbl through the adaptor protein. cbl-associated protein (CAP). A downstream effector of the CAP/cbl pathway is teratocareinoma 10 (TC 10), a member of the Rho family of GTpases. Clone#38 was discovered as a protein that interacts with the syntaxin 4-interacting protein (synip) in a yeast two-hybrid screening. Synip is a negative regulator of syntaxin 4, the receptor for GLUT4 vesicle docking at the plasma membrane. Interestingly, this novel protein posses a RhoGAP domain that interacts with TC10. In addition, it also possesses a PX and SH3 protein interaction domains that are important for binding of signaling molecules. Thus, our hypothesis is that clone#38 is a scaffolding protein that recruits insulin signaling molecules to the site of GLUT4 vesicle docking. To test this hypothesis, I will first biochemically characterize clone#38 interaction with synip and TC10. Deletional mutants that fail to interact with synip or TC10 will be used in specific aim 2 to evaluate the role of clone#38 in insulin-stimulated glucose uptake and GLUT4 translocation. In specific aim 3, I will search for proteins that bind to the PX and SH3 domains of clone#38. This approach may lead to new insights into the molecular mechanism of insulin action.

说明：（由申请人提供）胰岛素刺激葡萄糖摄取