Vincent Tagliabracci | Expanding the kinome

My laboratory has made major contributions to our understanding of non-canonical functions for protein kinases by discovering diverse and unanticipated biochemical activities that are performed by this protein superfamily. Protein kinases have been studied for decades and play important roles in many physiological and pathological processes. The textbook view is that these enzymes transfer phosphate from ATP to protein substrates in a process termed phosphorylation. However, my laboratory has overturned this paradigm by discovering new catalytic activities of atypical protein kinases and pseudokinases. For example, we discovered that the predicted pseduokinases SelO, SidJ and nsp12 catalyze AMPylation, polyglutamylation and mRNA capping, respectively. These results have revealed important new insights into the cellular response to oxidative stress and the pathogenic mechanisms employed by bacterial and viral pathogens. Our work on eukaryotic, prokaryotic, and viral kinases has exposed the catalytic versatility of the protein kinase fold and suggests that pseudoenzymes should be analyzed for alternative catalytic activities. In this lecture, I will present our recent discovery of kinases responsible for isoprenoid salvage.