NSF Young Investigator

在所有细胞的刺激/反应耦合中也使用了类似的分子策略。这个过程一般涉及位于细胞表面的跨膜受体和一系列细胞内信号转导蛋白，这些蛋白将信息从受体传递到介导特定反应的靶蛋白。细菌趋化性是研究受体介导的信号转导分子机制的理想模型系统。该系统由少量成分组成；一个跨膜受体蛋白家族、两个受体修饰酶、鞭毛运动器和四个细胞质信号转导蛋白，它们处理将受体信号与运动反应联系起来的信息。趋化作用中的中央信号转导机制涉及从组氨酸蛋白激酶CHEA到控制鞭毛旋转方向的磷酸化激活的调节蛋白CHEY的磷酸转移。该激酶CHEA的自动磷酸化受受体的调节，该机制需要辅助蛋白CHECT，并且依赖于受体配体的占位程度和受体的修饰状态。该系统为阐明调节生物化学中蛋白质修饰反应和蛋白质/蛋白质相互作用的基本原理提供了机会。细菌趋化性模型系统中信号转导的分子描述对于理解信号放大和适应等复杂调控现象的基本化学策略至关重要。斯托克博士的实验室正在使用分子遗传学、生化和生物物理方法相结合的方法来关联几种信号转导蛋白的结构和功能。

Similar molecular strategies are used in stimulus/response coupling in all cells. The process generally involves transmembrane receptors located at the cell surface and a set of intracellular signal transduction proteins that carry information from the receptors to the target proteins that mediate the specific responses. Bacterial chemotaxis is an ideal model system for investigating the molecular mechanism of receptor-mediated signal transduction. The system is composed of a small number of components; a family of transmembrane receptor proteins, two receptor modifying enzymes, the flagellar motor apparatus, and four cytoplasmic signal transduction proteins that process information linking receptor signaling to the motor response. The central signal transduction mechanism in chemotaxis involves phosphotransfer from a histidine protein kinase, CheA, to a phosphorylation-activated regulator protein that controls the direction of flagellar rotation, CheY. Autophosphorylation of the kinase, CheA, is regulated by the receptors in a mechanism that requires the auxiliary protein, CheW, and is dependent on both the degree of receptor ligand occupancy, and on the modification state of the receptor. The system provides an opportunity for elucidating the fundamental principles of protein modification reactions and protein/protein interactions in regulatory biochemistry. %%% A molecular description of signal transduction in the model system of bacterial chemotaxis is critical to understanding the fundamental chemical strategies for complex regulatory phenomena such as signal amplification and adaptation. Dr. Stock's laboratory is using a combination of molecular genetic, biochemical, and biophysical methods to correlate structure and function of several signal transduction proteins.