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The a-catulin/dystrophin-associated protein complex regulates GPCR function

α-catulin/肌营养不良蛋白相关蛋白复合物调节 GPCR 功能

基本信息

批准号：
9035401
负责人：
Chris S Hague
金额：
$ 29.36万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-07 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9035401
关键词：
Adrenergic Agents Adrenergic Receptor Affect Afghanistan Amino Acids Arterial Fatty Streak Benign Benign Prostatic Hypertrophy Binding Biological Assay Blood Vessels Cardiovascular Diseases Cell Culture Techniques Cells Collaborations Complex Couples Coupling Data Distal Drug Targeting Drug usage Dystrophin Dystrophin-Associated Protein Complex Elderly Epinephrine Family G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Genetic Screening Glutamate Receptor Goals Histamine Receptor Hormones Human Hybrids Hypertension Hypertrophy Immunoprecipitation Ion Channel Iraq Malignant Hypertension Maps Mass Spectrum Analysis Membrane Proteins Migraine Modeling Molecular Norepinephrine Pathway interactions Pharmaceutical Preparations Phospholipase C Phosphotransferases Post-Traumatic Stress Disorders Proteins Proteomics Receptor Activation Recruitment Activity Reporting Role Safety Sequence Analysis Serum Response Factor Shapes Signal Pathway Signal Transduction Signaling Molecule Signaling Protein Somatostatin Receptor Stable Isotope Labeling Stroke Techniques Testing Utrophin Veterans Vinculin Yeasts alpha catenin base beta-2 Adrenergic Receptors cell motility chemokine receptor cohort combat dystrobrevin fighting hypertension treatment in vivo male member neuron loss new therapeutic target novel prevent protein function receptor receptor function restenosis rho scaffold syntrophin therapeutic target vascular smooth muscle cell migration

项目摘要

DESCRIPTION (provided by applicant): α1-adrenergic receptors (ARs) are G-protein coupled receptors (GPCRs) that respond to sympathetic hormones norepinephrine and epinephrine, and are therapeutic targets for the treatment of hypertension, benign prostrate hypertrophy (BPH), and post-traumatic stress disorder (PTSD). α1-ARs comprise 3 unique subtypes, α1A, α1B, and α1D, which are ubiquitously expressed on blood vessels throughout the CNS. Although each subtype responds to norepinephrine/epinephrine and activates Gαq/11 signaling, the α1D-AR subtype performs a specialized role using mechanisms distinct from the α1A-AR and α1B-AR subtypes. For example, α1D-ARs stimulate vascular smooth muscle cell migration, while the α1A and α1B-AR subtypes stimulate vascular smooth cell hypertrophy. The molecular mechanisms that permit α1D-ARs to selectively activate pathways distinct from those used by the α1A and α1B-AR subtypes remains a major mystery in the field. Revealing the molecular mechanisms α1D- ARs use to stimulate vascular smooth cell migration will identify new drug targets to treat CNS blood vessel restenosis and atherosclerotic plaque formation, prevent migraine associated with malignant hypertension and reduce the potential for stroke and neuronal cell death.

描述（由申请人提供）：α1-肾上腺素能受体（ARs）是对交感激素去甲肾上腺素和肾上腺素有反应的g蛋白偶联受体（gpcr），是治疗高血压、良性前列腺肥大（BPH）和创伤后应激障碍（PTSD）的治疗靶点。α1-ARs包括α1A、α1B和α1D 3种独特的亚型，它们在整个中枢神经系统的血管中普遍表达。虽然每个亚型都对去甲肾上腺素/肾上腺素有反应并激活g - αq/11信号，但α1D-AR亚型发挥的特殊作用与α1A-AR和α1B-AR亚型不同。如α1D-ARs刺激血管平滑肌细胞迁移，而α1D-ARs则刺激血管平滑肌细胞迁移