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

mTORC2 signaling in metabolism and cell fate

mTORC2 信号在代谢和细胞命运中的作用

基本信息

批准号：
10584549
负责人：
Estela Jacinto
金额：
$ 32.66万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584549
关键词：
Affect Aging Amino Acids Anabolism Autoimmunity Cell Fate Control Cell Proliferation Cell Surface Proteins Cells Cellular Metabolic Process Complex Development Diabetes Mellitus Disease Environment Enzymes Eukaryota FRAP1 gene Flow Cytometry Gene Expression Generations Growth Growth Factor Hexosamines Insulin Lipids Malignant Neoplasms Messenger RNA Metabolic Metabolism Methods Modeling Mus Natural Compound Nutrient Nutrient availability Pathway interactions Phase Production Protein Biosynthesis Protein Kinase Proteins Proteomics Quantitative Reverse Transcriptase PCR Regulation Role Signal Transduction Signaling Molecule Sirolimus Starvation Supplementation Surface T-Cell Development T-Cell Receptor T-Lymphocyte T-cell receptor repertoire Thymocyte Development Thymus Gland Translating Western Blotting cell growth experimental study extracellular glycosylation innovation insight mouse model nutrient metabolism pharmacologic progenitor programs protein complex protein folding receptor response restraint therapeutically effective transcriptome sequencing

项目摘要

ABSTRACT Cell fate is influenced by the interplay of signals from the extracellular and intracellular environment. Studies over the years have revealed how the quality and quantity of signals triggered extracellular growth receptors mobilize intracellular signaling molecules leading to gene expression changes that dictate cell responses or fate. How such signals affect nutrient metabolism and how nutrient metabolites in turn control intracellular signaling, gene expression and ultimately cell fate remains poorly understood. A central signaling molecule that responds to nutrients and controls metabolism is mTOR. mTOR is an atypical Ser/Thr protein kinase that forms two protein complexes, mTORC1 and mTORC2. Numerous studies have focused on mTORC1, which is inhibited by the natural compound, rapamycin. mTORC1 is active in the presence of amino acids and promotes anabolic metabolism. In contrast to mTORC1, the regulation and functions of mTORC2 are poorly understood. In higher eukaryotes, mTORC2 is activated by growth factors such as insulin. Our project will elucidate how mTORC2 is involved in determining cell fate via its role in metabolic reprogramming during nutrient fluctuations. We will focus on how mTORC2 regulates the hexosamine biosynthetic pathway to control early thymocyte development. Our findings have implications for understanding how metabolism impacts cellular differentiation particularly in early T cell development. A deeper understanding of the regulation and functions of the mTOR complexes is needed for more effective therapeutic strategies against metabolic aberrations that occur during aging and diseases such as autoimmunity, diabetes and cancer.

摘要