Sensor kinase regulation in caulobacter differentiation

柄杆菌分化中的传感器激酶调节

• 批准号: 7118887
• 负责人: AUSTIN NEWTON
• 金额: $ 5.35万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118887
• 关键词: Caulobacter; aerobic bacteria; bacterial genetics; bacterial proteins; biological signal transduction; cell biology; cell cycle; cell cycle proteins; cell differentiation; cell growth regulation; cell morphology; enzyme activity; enzyme mechanism; gram negative bacteria; immunoprecipitation; laboratory rabbit; molecular biology; phosphorylation; protein kinase; protein localization; protein sequence; site directed mutagenesis; yeast two hybrid system

DESCRIPTION (provided by applicant): Asymmetric cell division is a fundamental mechanism for differentiation and the generation of new cell types. The gram negative, alpha-proteobacterium Caulobacter crescentus follows an invarient pattern of unequal cell division to produce two progeny cells with different structures and developmental fates. This organism is now recognized as an ideal model system for the study of how cellular asymmetry is established and its role in developmental regulation. An understanding of these processes is the long-term goal of the research proposed in this application. Genetic analysis has shown that developmental events in these cells are tightly coordinated with cell cycle progression by networks of essential signal transduction pathways mediated by the two-component family of proteins. Remarkably, the sensor kinases that initiate these pathways are, like the morphogenic events they control, spatially localized at the cell poles. A central focus of the proposed work is to understand the molecular mechanisms responsible for the subcellular localization of the PleC, DivJ, DivL and CckA kinases and the role of localization in kinase function and regulation. The aims of the proposed experiments are to: (1) carry out a detailed genetic and biochemical analysis of the PleC kinase and its cognate essential response regulator DivK to define their roles in the regulation of polar morphogenesis and cell division; (2) identify the sequences within PleC and other cell cycle-regulated kinases that specify their subcellular localization and examine the role of localization in developmental regulation; and (3) identify elements of the cellular machinery responsible for subcellular localization of these signal transduction proteins.

描述（由申请人提供）：不对称细胞分裂是分化和产生新细胞类型的基本机制。革兰氏阴性α-变形杆菌新月柄杆菌遵循不变的不均等细胞分裂模式，产生具有不同结构和发育命运的两个子代细胞。这种生物体现在被认为是研究细胞不对称性如何建立及其在发育调节中的作用的理想模型系统。理解这些过程是本申请中提出的研究的长期目标。遗传分析表明，这些细胞中的发育事件与细胞周期进程紧密协调，由双组分蛋白质家族介导的基本信号转导途径网络。值得注意的是，启动这些途径的传感器激酶，就像它们控制的形态发生事件一样，在空间上定位于细胞两极。拟议工作的一个中心焦点是了解负责PleC，DivJ，DivL和CckA激酶的亚细胞定位的分子机制，以及定位在激酶功能和调节中的作用。所提出的实验的目的是：（1）对PleC激酶及其同源的必需反应调节因子DivK进行详细的遗传和生化分析，以确定它们在极性形态发生和细胞分裂的调节中的作用;（2）鉴定PleC和其他细胞周期调节激酶中指定其亚细胞定位的序列，并检查定位在发育调节中的作用;和（3）鉴定负责这些信号转导蛋白的亚细胞定位的细胞机制的元件。