权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Functional Role of the PXL Domain of SGK1 in Epithelial Sodium Transport

SGK1 PXL 结构域在上皮钠转运中的功能作用

基本信息

批准号：
7166073
负责人：
ALAN C PAO
金额：
$ 9.07万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7166073
关键词：
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one Advisory Committees Aldosterone Apical Binding Biochemistry Biological Assay Blood Pressure Cell membrane Cell physiology Cells Cellular biology Clinical Complement Computer Simulation Condition Confocal Microscopy Country Cultured Cells Data Defect Development Distal Environment Epidemic Epithelial Epithelial Cells Exposure to Extracellular Fluid Goals Hyperinsulinism Hypertension In Vitro Insulin Insulin Resistance Ion Transport Ions Kidney Laboratories Lead Life Lipids Location Maintenance Mediating Mediator of activation protein Membrane Mentors Metabolic Molecular Mus N-terminal Nephrology Nephrons Obesity Oocytes Pathway interactions Pattern Phosphatidylinositols Phospholipids Phosphorylation Phosphotransferases Physicians Play Rate Regulation Research Research Personnel Research Training Resources Role Scientist Sgk protein Signal Pathway Signal Transduction Site Site-Directed Mutagenesis Sodium Staining method Stains Structure Surface Syndrome System Technical Expertise Testing Threonine Training Programs Transcriptional Regulation Xenopus laevis apical membrane base career design epithelial Na+ channel hormone regulation in vivo mutant novel programs protein aminoacid sequence research study response trafficking

项目摘要

DESCRIPTION (provided by applicant): The role of insulin in controlling sodium (Na+) reabsorption in the kidney is of particular clinical importance due to its relevance to hypertension associated with the metabolic (insulin resistance) syndrome. Hyperinsulinemia can lead to inappropriate renal Na+ handling, resulting in hypertension. A major site of insulin's action is on the epithelial Na+ channel (ENaC) found in the aldosterone-sensitive distal nephron. Insulin, through the phosphatidylinositide 3'-kinase (PI3K) signaling pathway, activates serum and glucocorticoid regulated kinase 1 (SGK1), which plays a key role in stimulating ENaC accumulation at the apical membrane of the principal cell. SGK1 appears to have a novel lipid interaction motif (PXL domain) that may participate in SGK1 activation by insulin. The broad objective of this proposal is to elucidate the mechanistic basis of how SGK1 is activated by the insulin-PI3K signaling pathway. The aims are the following: (1) Identify which phosphoinositides are functionally important for SGK1's ability to stimulate ENaC transport; (2) Evaluate whether the PXL domain is required for SGK1 activation; (3) Determine whether the PXL domain regulates SGK1 activation through membrane targeting. The elucidation of these pathways will likely identify novel avenues of treatment for this form of hypertension, which will undoubtedly become more prevalent with the rising obesity epidemic in our country. In addition to the proposed experiments, didactic coursework in biochemistry, cell biology, and the responsible conduct of research will complement a structured research training program to assist the candidate in achieving his long term goal for an academic career as a physician-scientist in nephrology. Dr. David Pearce, who is a leader in the field of hormone regulation of ion transport, will mentor the candidate's scientific development. Moreover, Dr. Stephen Gluck, a highly respected expert in cellular physiology of ion transporters, and Dr. Keith Mostov, and internationally recognized expert in epithelial cell trafficking, will provide scientific expertise in the design of experiments and interpretation of results. A professional development advisory committee will also convene at regular intervals to provide scientific and career support. UCSF offers the scientific expertise and the technical resources to provide an ideal environment for preparing this candidate for a successful career as a physician-scientist.

描述（由申请人提供）：