SIGNAL TRANSDUCTION IN CAULOBACTER CELL CYCLE REGULATION

细胞分裂不均是产生新细胞类型的核心机制。在新月桂杆菌中，分化是细胞反复不对称分裂的直接结果，这种水生细菌为阐明发育控制的机制提供了一个理想的模型。这些细胞的分化模式和细胞周期进程由两组分的信号转导系统密切协调。这些双组分蛋白质可能的独特之处在于，它们对内部细胞周期信号而不是环境条件做出反应，其中一些对分裂和细胞活力是必不可少的。然而，信号转导通路的组织结构还没有完全确定，这些通路如何协调细胞周期中发育事件的精确时间和空间模式还远不清楚。该建议中描述的实验旨在解决以下目标：1.确定并表征调控细胞周期进展和分化的基本信号转导途径DivJ=&gt；DivK=&gt；X=&gt；CtrA；2.确定基本反应调节因子DivK如何在信号转导途径(S)中发挥作用，控制细胞分裂和运动；3.表征酪氨酸激酶DivL在信号转导中的作用机制和功能；4.分析组氨酸激酶DivJ和反应调节因子DivJ在确定细胞极性中的作用；5.通过参与CtrA磷酸化和激活的重要信号转导通路，在体内检测细胞分裂基因的调控。

Unequal cell division is a central mechanism in the generation of new cell types. In Caulobacter crescentus differentiation is the direct result of repeated, asymmetric cell division and this aquatic bacterium provides an ideal model for elucidating the mechanisms underlying developmental control. The patterns of differentiation and cell cycle progression in these cells are closely coordinated by two- component signal transduction systems. Possibly unique aspects of these two-component proteins is the fact that they respond to internal cell cycle cues instead of environmental conditions and some of them are essential for division and cell viability. The organization of the signal transduction pathways is not fully defined, however, and how these pathways coordinate the precise temporal and spatial patterns of developmental events during the cell cycle is far from clear. Experiments described in the proposal are designed to address the following goals: I. Identify and characterize components in the essential signal transduction pathway, DivJ => DivK => X => CtrA, which regulates cell cycle progression and differentiation; 2. Determine how the essential response regulator DivK functions in a signal transduction pathway(s) to control both cell division and motility; 3. Characterize mechanism of action and function of tyrosine kinase DivL in signal transduction; 4. Analyze the roles of histidine kinase DivJ and response regulator PleD in establishing cellular polarity; and 5. Examine the regulation of cell division genes in vivo by the essential signal transduction pathway responsible for phosphorylation and activation of CtrA.