Faculty

SUSAN S. TAYLOR

Professor of Pharmacology and Chemistry & Biochemistry

TEL: 858-534-3677

FAX: 858-534-8193

email: staylor@ucsd.edu

website: http://chem-faculty.ucsd.edu/taylor/

Ph.D., Johns Hopkins University

Key Words: Protein kinases/signal transduction: structure/function and localization; biophysics; crystallography; NMR, fluorescence/FRET.

Our primary focus is to understand the structure, function and dynamics of cAMP-dependent protein kinase (PKA) using biochemical, biophysical and recombinant approaches. The Catalytic subunit crystal structure, solved in 1991, was the first protein kinase structure, and it continues to provide a prototype for all protein kinases. The folding as well as the location of conserved residues throughout the core is conserved through the kinase superfamily. Open and closed conformations provide an indication of the enzymes flexibility. Both ATP and peptide binding are clearly delineated and a transition state complex was recently solved. Kinetics, fluorescence and hydrogen/deuterium exchange are being used to define conformational changes, ligand binding sites, and sites of protein:protein interactions. The structures of the RI face="Symbol">a and RIIß regulatory subunits have also been solved, and reveal critical isoform-specific differences. The dimerization domain at the N-terminus serves also as a docking site for A Kinase Anchoring Proteins (AKAPs). The structure of the RI face="Symbol">a D/D domain was solved by NMR in collaboration with Dr. Patricia Jennings.

To probe kinase function in cells, we use fluorescently labeled proteins as well as plasmids encoding for GFP- or epitope tagged proteins. This allows us to look at subcellular localization, translocation, and to detect PKA activity in individual living cells. We are now characterizing the structure and subcellular localization of two novel AKAPs, DAKAP1 and DAKAP2, that bind to both RI and RII.

Selected Publications:

Molecular Basis for Regulatory Subunit Diversity in cAMP-dependent Protein Kinase: Crystal Structure of the Type IIß Regulatory Subunit. With T.C. Diller, Madhusudan, and N-h. Xuong. Structure 9, 73-82 (2001).

Domain Organization of DAKAP2 Revealed by Enhanced Deuterium Exchange-Mass Spectrometry (DXMS). With Y. Hamuro, L.L. Burns, J.M. Canaves, R.C. Hoffman, and V.L. Woods, Jr. J. Mol. Biol. 321, 703-714 (2002).

A 15-residue bi-functional element in DAKAP1 is required for both ER and mitochondrial targeting. With Y. Ma. J. Biol. Chem. 277, 27328-27336 (2002).

Regulation of cAMP dependent Protein Kinase Activity by Glutathionylation. With K.M. Humphries and C. Juliano. J. Biol. Chem. 277, 43505-43511 (2002).

Amide H/²H Exchange Reveals Communication Between the cAMP-and Catalytic Subunit-Binding Sites in the RI face="Symbol">a Subunit of Protein Kinase A. With G.S. Anand, C.A. Hughes, J.M. Jones, and E.A. Komives. J. Mol. Biol. 323, 377-386 (2002).

Designing Isoform-Specific Peptide Disruptors of Protein Kinase A Localization. With L. L. Burns-Hamuro, Y. Ma, S. Kammerer, U. Reineke, C. Self, C. Cook, G. Olson, C.R. Cantor, and A. Braun. PNAS 100, 4072-4077 (2003).

Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structure. With P. Akamine, Madhusudan, J. Wu, and N.H. Xuong. J. Mol. Biol. 327, 159-171(2003).