Mechanistic studies of protein kinases

PROJECT SUMMARY This research focuses on a class of enzymes that are integral to human health, protein kinases. The most frequent post-translational modification of proteins is phosphorylation, and these modifications made by protein kinases. These additions are an integral component of the information flow controlled by numerous signaling pathways that control a myriad of cellular decisions ranging from cell growth to immune responses. Disruption of these pathways leads to diseases ranging from cancer to developmental defects. The goal of this research program is to determine the molecular mechanisms that regulate the activity of protein kinases. We will use the Hippo pathway, which controls decisions of cell fate and number, as a model system to investigate different mechanisms that modulate the activity of protein kinases. We will combine biophysical, biochemical, structural bioinformatics, and cellular approaches to examine how the activity of these enzymes is tuned. This work will address fundamental gaps in our understanding of protein kinase regulation, decipher the molecular mechanisms regulating the activity of the protein kinases in the Hippo pathway, and investigate novel routes of Hippo pathway modulation. The molecular insight gained from this research will accelerate the development of targeted therapies to block inappropriate kinase activity which will be broadly applicable to multiple diseases.