CAREER: Identification of Kinase Substrates using Selective Irreversible Crosslinkers

CBET-0744413，灰色我们细胞最常见的交流方式之一是通过使用被称为磷酸盐的化学信使。磷酸盐由“蛋白激酶”护送通过细胞，并且只能通过这些蛋白的作用从一种蛋白质转移到另一种蛋白质。当一种激酶将一种磷酸盐添加到特定的蛋白质中时，它实质上是指示该蛋白质执行特定的功能。我们的基因组编码500多个激酶，其中许多与疾病有关。为了充分了解细胞如何交流，以及如何修复通讯不畅的病态细胞，有必要发现从激酶接收磷酸盐“信息”的全套蛋白质。这项研究项目是开发一种化合物，这种化合物将人为地使给定的激酶粘连到它正在转移磷酸盐的蛋白质上。这些所谓的“交联”化合物将创建一份全面的清单，列出哪些蛋白质被哪些酶磷酸化。根据这些信息，研究人员可以创建所有主要细胞信号通路的路线图，这反过来将为理解生物系统和发现新的药物靶点提供关键信息。作为外展活动，PI计划指导促进翻译研究的内科科学家。作为一个教育组成部分，PI将创建纳米班级，并为那些对科学感兴趣的人协调外展活动。

CBET-0744413, GrayOne of the most common ways our cells communicate is through the use of chemical messengers known as phosphates. Phosphates are escorted through the cell by "protein kinases" and can only be transferred from one protein to another through the actions of these kinases. When a kinase adds a phosphate to a particular protein, it essentially instructs that protein to perform a specific function. Our genome encodes for over 500 kinases and many of these kinases have been implicated in disease. In order to fully understand how cells communicate, and how to fix diseased cells that are mis-communicating, it is necessary to discover the full set of proteins that receive phosphate "messages" from kinases. The research project is to develop compounds that will artificially cause a given kinase to become stuck to the protein to which it is transferring a phosphate. These so-called "cross-linking" compounds will create a comprehensive inventory of which proteins are phosphorylated by which kinases. From this information the investigators can create a roadmap of all major cell signaling pathways , which will in turn provide crucial information for understanding biological systems and for discovering new drug targets. As the outreach activity, the PI plans to mentor physician scientists facilitating translational research. AS an educational component, the PI will create nanoclasses as well as coordinate outreach activities for those interested in science.