METABOLIC SIGNALS DRIVING CELL GROWTH & PROLIFERATION

驱动细胞生长的代谢信号

基本信息

批准号：
9027703
负责人：
Benjamin P Tu
金额：
$ 36.94万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9027703
关键词：
Accounting Amino Acids Automobile Driving Autophagocytosis Catalytic Domain Cell Proliferation Cells Complex Data Defect Enzymes Event Exhibits Funding Genetic Growth Homeostasis Human Link Logic Mammalian Cell Metabolic Methionine Methylation Methyltransferase Modification Nutrient Pathway interactions Phenotype Phosphopeptides Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Play Post-Translational Protein Processing Protein Dephosphorylation Protein phosphatase Proteins Proteomics Regulation Request for Applications Research Personnel Role S-Adenosylmethionine Signal Transduction Signaling Protein Sirolimus System Yeasts cancer cell cancer type cell growth cell growth regulation cell type chemical genetics demethylation genetic selection high throughput screening in vivo inhibitor/antagonist insight interest mutant novel phosphoproteomics public health relevance response small molecule inhibitor uptake

项目摘要

DESCRIPTION (provided by applicant): The major cellular phosphatase Protein Phosphatase 2A (PP2A) is regulated by an unconventional but conserved methylation modification on the very carboxy terminus of its catalytic subunit. However, the functional role of this methylation remains incompletely understood. In the current funding period, it was shown that this methylation modification on PP2A is responsive to intracellular methionine and SAM levels. As such, the amino acid methionine and its downstream metabolite SAM are able to promote the methylation of PP2A and thereby influence the activity of the phosphatase against particular substrates in cellular signaling and growth control. This renewal application proposes to comprehensively investigate the in vivo functions of the methylation of PP2A using a combined genetic, chemical, and proteomic approach. It is notable that this modification on PP2A enables it to function as an amino acid-responsive, metabolically-regulated phosphatase which could impact the phosphorylation status of many important signaling proteins in tune with the metabolic state of the cell.

描述（由应用提供）：主要的细胞磷酸酶蛋白磷酸酶2a（PP2A）受其催化亚基的羧基末端的非常规但构成甲基化的调节。然而，这种甲基化的功能作用仍未完全理解。在当前的资金期间，这表明对PP2A的这种甲基化修饰对细胞内甲基化和SAM水平有反应。因此，氨基酸甲基甲酸盐SAM能够促进PP2A的甲基化，从而影响磷酸酶对特定底物在细胞信号传导和生长控制中的活性。该更新应用建议，以全面研究PP2A甲基化的体内功能，使用遗传，化学和蛋白质组学方法组合。值得注意的是，PP2A上的这种修饰使其能够充当氨基酸反应性，代谢性调节的磷酸酶，这可能会影响许多重要的信号蛋白的磷酸化状态，从而与细胞的代谢状态调节。