Chemical probes of signal-transducing proteins.

Protein kinases are key participants in signal transduction pathways. A direct assessment of the relationship between the activity of any given protein kinase and the corresponding cellular phenotype has proven challenging. This is due to the large number of protein kinases encoded by the human genome coupled with intracellular temporal and spatial constraints that appear to further regulate the ultimate response of a cell to a stimulus. Our work has focused on the development of chemical probes to address the complexities associated with protein kinase-mediated cell signaling. These include the acquisition of highly selective substrates and inhibitors for specific members of the protein kinase family, the design and synthesis of light-activated signaling proteins and their corresponding inhibitors, and the preparation of fluorescent reporters of intracellular protein kinase action.