Skip to main content
FACULTY PROFILE STYLESHEET: do not remove this block

Susan Taylor, Ph.D.

Distinguished Professor of Pharmacology, Chemistry & Biochemistry

Susan Taylor, Ph.D.

Susan Taylor, Ph.D.
Distinguished Professor of Pharmacology, Chemistry & Biochemistry

Research Interests  

            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.

 

Selected Publications

“Isoform-specific Subcellular Localization and Function of Protein Kinase A Identified by Mosaic Brain Mapping” Ilouz, R., Lev-Ram, V., Bushong, E.A., Stiles, T., Friedmann-Morvinski, D., Douglas, C., Goldberg, G., Ellisman, M.H. and Taylor, S.S.  eLife 6:e17681 (2017).

“Turning the “Violin” of Protein Kinases: The Role of Dynamics-based Allostery” Ahuja, L.G., Taylor, S.S. and Kornev, A.P.  IUBMB Life 71:685-96 (2019)

 “Structural analyses of the PKA RIIβ holoenzyme containing the oncogenic DnaJB1-PKAc fusion protein reveal protomer asymmetry and fusion-induced allosteric perturbations in fibrolamellar hepatocellular carcinoma”. Lu, T.-W., Aoto, P.C., Weng, J.-H., Nielsen, C., Cash, J.N., Hall, J., Zhang, P., Simon, S.M., Cianfrocco, M.A. and Taylor, S.S. Plos Biol.  (2020)

“PKA Cβ: A forgotten catalytic subunit of cAMP-dependent protein kinase opens new windows for PKA signaling and disease pathologies” Taylor, S. S., Walbott, M., Machal, E. M. F., Søberg, K., Ahmed, F., Bruystens, J., Vu, L., Baker, B., Wu, J., Raimondi, F., Ongeri, E. M.,Herberg, F. W. and Skålhegg, B. S. Biochem. J. 478:2101-2119 (2021)

“Subcellular localization of PKA catalytic subunits provides a basis for their distinct functions in the retina” Roa, J. N., Ma, Y., Mikulski, Z., Xu, Q., Ilouz, R., Taylor, S.S. and Skowronska-Krawczyk, D. Frontiers in Molecular Neuroscience 14:782041 (2021)

“LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains.” Weng JH, Aoto PC, Lorenz R, Wu J, Schmidt SH, Manschwetus JT, Kaila-Sharma P, Silletti S, Mathea S, Chatterjee D, Knapp S, Herberg FW, Taylor SS. PLoS Biol. 20:e3001427. doi: 10.1371/journal.pbio.3001427. eCollection (2022)

Divisions

Neuropharmacology & Neurological Disorders

Programs

Signaling & Molecular Pharmacology
Biochemical, Biophysical and Structural Pharmacology

CONTACT

(858) 534-3677
staylor@ucsd.edu

Websites

UCSD Profile