The Taylor lab uses interdisciplinary approaches to study the structure and function of protein kinases. We use cAMP-dependent protein kinase (PKA) as a prototype for the protein kinase superfamily, which is one of the largest gene families and a major target for drug discovery. Our structure of the PKA catalytic (C) subunit, solved in 1991, was the first protein kinase structure and in the intervening decades we have learned much about the catalytic machinery and the dynamic hydrophobic core architecture that mediates allosteric regulation. Most rules elucidated from PKA apply to the whole family and provide a framework for drug discovery overall. In parallel with our structural, biophysical, and computational simulation studies we are developing tools that allow us to probe protein kinases in cells. Being able to follow the dynamic behavior of organelles such as the mitochondria allow us to create a real time image of how protein phosphorylation regulates biological processes in live cells, while mosaic imaging of PKA isoforms in the brain highlights the importance of isoform-specific spatial and temporal organization.

Isoform specificity is another focus of the Taylor laboratory. The active PKA Ca-subunit is assembled as a tetrameric holoenzyme with four functionally non-redundant R-subunit dimers. To appreciate allosteric regulation and the functional non-redundancy of the PKA holoenzymes it is essential to visualize the full-length R2C2 holoenzymes. Most recently we are exploring the functional non-redundancy of the understudied Cb subunits, which is the forgotten PKA isoform even though ~50% of PKA signaling in neurons is mediated by Cb. Using the retina as a window into the brain we are exploring the localization of the PKA isoforms.