CBC Colloquium: "Lessons Learned from PKA: Building Molecular Communities"Thu, 1/23/2020 - 4:00pm
Protein phosphorylation is critical for regulation in eukaryotic cells. The human genome encodes more than 500 protein kinases, making this one of the largest gene families. Although very diverse in how they receive and transmit signals, all protein kinases share a conserved catalytic core. While it is essential to understand how these enzymes function as catalysts, it is equally important to understand how they are regulated, how they function as scaffolds, and how they are localized.
Studying the structure and function of cAMP-dependent protein kinase (PKA), one of the simplest members of the protein kinase family, is our primary focus. Our initial chemical studies eventually led to solving the crystal structure of PKA in 1991; this structure continues to serve as a prototype for the entire family. In parallel, we solved structures of the regulatory subunits which are the major receptors for cAMP in mammalian cells. Recent holoenzyme structures revealed for the first time how the catalytic subunit is regulated. Structures of A kinase-anchoring protein (AKAP) motifs bound to the regulatory subunits explain the molecular basis for targeting of PKA. An underlying theme of our laboratory is the iterative use of biophysical, biochemical, and biological approaches to probe PKA structure and function at both the atomic and cellular levels.