CAREER: Identification of Kinase Substrates using Selective Irreversible Crosslinkers

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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.