Susan Taylor Ph.D. (Angeline Lyon and Nick Noinaj)
Professor of Chemistry and Biochemistry and Professor of Pharmacology
University of California, San Diego

“Lessons Learned from PKA: From Molecules to Cells”

Cyclic AMP-dependent protein kinase (PKA) has served as the prototypical protein kinase for the large protein kinase superfamily that regulates so much of biology. One of the most remarkable features of that first protein kinase structure, solved over 25 years ago, was its G-Loop, which is functionally and structurally distinct from the classic Rossmann/Walker P-Loop. Embedded in this loop are the fundamental features that define the protein kinases as highly regulated molecular switches in contrast to classic metabolic enzymes that have evolved to be efficient catalysts. The PKA catalytic (C) subunit is regulated by a set of four functionally non-redundant cAMP-binding regulatory (R) subunits that are assembled as inactive (R2C2) holoenzymes at discrete sites in the cell, typically as part of a macromolecular complex and in close proximity to a specific substrate. To fully understand and appreciate allosteric PKA signaling and how dysfunctional PKA signaling can lead to disease, it is thus essential to understand not just at the structure of the kinase but also the structure and functional differences of each holoenzyme as well as the targeted localization of each isoform to specific signalosomes within the cell.