Molecular mechanisms of adiponectin signaling and PAQR function

脂联素信号传导和 PAQR 功能的分子机制

基本信息

批准号：
9144473
负责人：
Andrew Kruse
金额：
$ 42.38万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9144473
关键词：
Address Affinity Agonist Animal Model Antibodies Area Attention Bacteria Binding Biochemical Biological Biology Cardiovascular Diseases Cell membrane Cells Cellular Assay Ceramidase Ceramides Complex Crystallization Crystallography Data Development Diabetes Mellitus Diabetic mouse Engineering Environment Enzymes Event Exhibits Family Family member Genetic Screening Genetic study Goals Health Hormones Human Hydrolysis Insulin Integral Membrane Protein Ligand Binding Ligands Mediating Membrane Metabolic Methods Molecular Mus Neurotransmitters Non-Insulin-Dependent Diabetes Mellitus Obesity Organism Pathway interactions Pharmaceutical Preparations Phase Play Production Protein Engineering Proteins Reagent Receptor Signaling Research Resolution Role Second Messenger Systems Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Molecule Sphingosine Structure Therapeutic Uses Variant Work Yeasts adiponectin base cardiovascular health cytokine design high throughput screening insulin sensitivity new therapeutic target overexpression receptor second messenger small molecule targeted treatment therapeutic development tool

项目摘要

DESCRIPTION (provided by applicant): Transmembrane signaling plays a central role in all of biology, allowing cells to sense and respond to their environment. In humans, integral membrane receptors mediate the effects of hormones, neurotransmitters, cytokines, and a multitude of other signaling molecules. The PAQR receptors are a poorly characterized family of transmembrane receptors, found in organisms ranging from bacteria to humans. Recently, two PAQR receptors have attracted particular attention because they mediate the effects of a protein hormone called adiponectin. Adiponectin has been shown to induce profound insulin-sensitizing and cardioprotective effects in mouse models of diabetes and cardiovascular disease, but little is known regarding the molecular mechanisms of adiponectin signaling. To unravel the molecular details of adiponectin receptor signaling, we will pursue a combination of structural and biochemical studies of adiponectin and its receptors, with the long term goal of developing a detailed molecular understanding of signaling through the adiponectin receptors and broader PAQR family.

描述（由申请人提供）：跨膜信号传导在所有生物学中发挥着核心作用，使细胞能够感知并响应其环境。在人类中，整合膜受体介导激素、神经递质、细胞因子和多种其他信号传导的作用。 PAQR 受体是一个特征不明确的跨膜受体家族，存在于从细菌到人类的各种生物体中，最近，两种 PAQR 受体引起了特别关注，因为它们介导一种称为“蛋白质激素”的作用。脂联素已被证明可以在糖尿病和心血管疾病的小鼠模型中诱导深远的胰岛素增敏和心脏保护作用，但对于脂联素信号传导的分子机制知之甚少，我们将探究脂联素受体信号传导的分子细节。脂联素及其受体的结构和生化研究相结合，长期目标是通过脂联素受体和更广泛的 PAQR 对信号传导进行详细的分子理解家庭。