Susan Taylor

Bio: Dr. Susan Taylor is a professor of Chemistry and Biochemistry and Pharmacology at the University of California, San Diego, and is a Howard Hughes Medical Investigator. Dr. Taylor joined the UCSD faculty in 1972 and has since received numerous honors, fellowships and awards. She was elected a fellow of the American Academy of Arts and Sciences in 1992 and received the Forefronts of Large Scale Computation Award in 1993. She was elected into the National Academy of Sciences in 1996 and is a member of the National Institute of Medicine. She is a past president of the American Society of Biochemistry and Molecular Biology. She has served on the Board of Councils for the National Cancer Institute, for the Heart, Lung and Blood Institute and for NIDDK. She has also served on the General Medicine Council for NIH. Dr Taylor's research focuses on the structure and function of protein kinases and on the molecular basis for signal transduction. In 1991, Dr. Taylor and her group solved the 3-D crystal structure of the catalytic unit of cyclic-AMP-dependent protein kinase (CAPK). This was the first protein kinase structure to be solved and serves as the prototype for the kinase super-family. She uses an interdisciplinary approach to study the structure, function, and dynamics of PKA signaling.

Talk Title: Dynamics of Signaling by PKA

Abstract: cAMP-dependent protein kinase (PKA) is one of the best understood members of the protein kinase superfamily. This family accounts for nearly 2% of the human genome and includes many protein kinases that are closely linked to diseases such as diabetes and cancer. PKA, one of the simplest protein kinases, serves as a prototype for the entire superfamily. The dynamics of the catalytic (C) subunit as it binds its substrates and shuttles through its catalytic cycle has been elucidated at the structural level and in solution using fluorescence and hydrogen/deuterium exchange coupled with mass spectrometry. In addition to their role as catalysts, the protein kinases interact with many other proteins as they make and break extended intramolecular networks in response to outside signals. The inhibitors of PKA, both the regulatory subunits and PKI, are highly dynamic and modular proteins. Their dynamic behavior in solution has been mapped by H/D exchange, small angle Xray scattering, and by fluorescence. The crystal structure of a deletion mutant of the RI_ subunit reveals for the first time a highly dynamic process where the disordered linker region binds to an extended surface of the C-subunit and the Camp binding domain undergoes major regoranization of its helical subdomain. This structure provides a new paradigm for molecular recognition by a protein kinase where several inhibitors use a common autoinhibition mechanism of docking a pseudo substrate peptide to the active site cleft. Different surfaces are then utilized in novel ways to achieve high affinity binding. Additional complexity is added to PKA signaling by the scaffold proteins, the A Kinase Anchoring Proteins (AKAPs) that target PKA to specific subsites in the cell. The challenge of understanding signaling at these localized sites will require novel imaging tools that allow us to monitor kinase activity and second messenger formation in real time and space in living cells (supported by HHMI and grants from the NIH).