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

The role of TCTP in regulating adiponectin signaling

TCTP 在调节脂联素信号传导中的作用

基本信息

批准号：
9252443
负责人：
Lily Q Dong
金额：
$ 34.03万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
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：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9252443
关键词：
Adaptor Signaling Protein Adipose tissue Affect Alpha Cell Binding Binding Proteins Cardiovascular Diseases Cells Complex Complications of Diabetes Mellitus Data Development Diet Down-Regulation Energy Metabolism Fatty Liver Fibrosis Functional disorder Hepatic Hepatocyte Human Impairment Inflammation Insulin Resistance Knock-out Knockout Mice Laboratories Lead Leucine Zippers Liver Messenger RNA Metabolic Metabolic Diseases Molecular Mus Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity PH Domain PTB Domain Pathway interactions Patients Phosphorylation Physiological Pioglitazone Play Prevention strategy Protein Isoforms Proteins Reducing diet Regulation Resistance Role Signal Transduction TPT1 gene Testing Therapeutic Thermogenesis Thinness Time Tissues Treatment Efficacy Yeasts Yin-Yang adiponectin base cDNA Library glucose metabolism glucose production impaired glucose tolerance improved in vivo insulin sensitivity insulin sensitizing drugs lipid metabolism novel novel therapeutic intervention novel therapeutics obesity treatment overexpression prevent protein function public health relevance receptor scaffold screening transcription factor yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): Adiponectin has been well established as an insulin sensitizer to suppress glucose production and regulate hepatic lipid metabolism. However, the molecular mechanisms underlying adiponectin action remain largely unknown. Our laboratory identified for the first time an adiponectin receptor interactive protein, APPL1, which plays an essential role in adiponectin signaling. Subsequently, we showed that APPL2, an isoform of APPL1, acts as integrated Yin-Yang regulatory machinery with APPL1 to regulate adiponectin signaling in cells. To elucidate the mechanisms by which APPL isoforms regulate adiponectin signaling, we screened a yeast two-hybrid cDNA library using APPL2 as bait. This screening led to identification of TCTP as a binding protein that interacts with APPL isoforms. Based on our preliminary studies, we hypothesize that TCTP is a key regulator of adiponectin signaling in the liver and its interaction with APPL isoforms may provide a mechanism underlying obesity-induced down-regulation of adiponectin signaling. Impairment of adiponectin signaling together with reduced level of adiponectin in obesity and type 2 diabetes play important roles in development of insulin resistance. Understanding the mechanisms underlying TCTP-regulated adiponectin signaling may lead to identification of novel and effective therapeutic strategies for the prevention and treatment of metabolic disorders.

描述（由申请方提供）：脂联素已被公认为抑制葡萄糖生成和调节肝脏脂质代谢的胰岛素增敏剂。然而，脂联素作用的分子机制仍不清楚。我们的实验室首次鉴定了脂联素受体相互作用蛋白APPL1，其在脂联素信号传导中起重要作用。随后，我们发现APPL2，APPL1的一种异构体，作为与APPL1整合的阴阳调节机制来调节细胞中的脂联素信号。为了阐明APPL异构体调节脂联素信号转导的机制，我们以APPL 2为诱饵筛选了酵母双杂交cDNA文库。该筛选导致TCTP被鉴定为与APPL同种型相互作用的结合蛋白。基于我们的初步研究，我们假设TCTP是肝脏中脂联素信号传导的关键调节因子，其与APPL亚型的相互作用可能提供了肥胖诱导的脂联素信号传导下调的潜在机制。肥胖和2型糖尿病患者脂联素信号通路受损和脂联素水平降低在胰岛素抵抗的发生发展中起重要作用。了解TCTP调控脂联素信号传导的机制可能会导致识别新的和有效的治疗策略，用于预防和治疗代谢紊乱。