个人简介

2009 Vanderbilt Prize in Biomedical Sciences 2009 FASEB Excellence in Science Award 2008 Elected Fellow of the American Association for Advancement of Science (AAAS) 2007 ASBMB William C. Rose Award 2001 Garvan-Olin Medal, American Chemical Society 1997-pres Howard Hughes Medical Institute Investigator 1997 Elected into the National Academy of Sciences 1997 Elected into Institute of Medicine 1996 Edwin G. Krebs Lecture in Molecular Pharmacology, University of Washington, School of Medicine, Seattle 1994-1997 President-elect, President, past President, ASBMB 1994 Hans Lindner Memorial Lecture, The Weizmann Institute, Rehovot, Israel 1992 Elected into the American Academy of Arts and Sciences 1985-1990 Editorial Board, J. Biol. Chem

研究领域

Biochemistry

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 (C) subunit was the first protein kinase structure to be solved and continues to serve as a prototype for all protein kinases, now recognized as one of the largest gene superfamilies. In parallel with crystallography, kinetics, fluorescence, H/D exchange, and small angle Xray/neutron scattering are used to define conformational changes, ligand binding sites, and sites of protein:protein interaction. Structures of RIα and RIIβ regulatory subunits reveal critical isoform-specific differences. Most recently holoenzyme complexes were solved for RIα, RIIα, and RIIβ, and these reveal major conformational changes in the R subunits as they release cAMP and bind to the C subunit. Based on SAXS, the architecture of the holoenzymes differ significantly. The dimerization domain at the R-subunit N-terminus serves as a docking site for A Kinase Anchoring Proteins (AKAPs). Structures of the D/D domains for RIα and RIIα were solved by NMR and by crystallography, respectively. Plasmids encoding for GFP-tagged proteins are used to probe kinase function in cells. This allows us to look at subcellular localization and translocation, and to detect PKA activity in individual living cells. We are now characterizing the structure and subcellular localization of two novel AKAPs, D-AKAP1 and D-AKAP2, that bind to both RI and RII. D-AKAP1 targets PKA to the outer mitochondrial membrane while D-AKAP2, which binds to PDZ domains and Rab 4/11, is involved in late endocytosis.

近期论文

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Eggers CT, Schafer JC, Goldenring JR, Taylor SS, "D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling.", J Biol Chem, 2009, Vol. 284, Issue 47, 32869-80 [View Abstract] Kornev AP, Taylor SS, Ten Eyck LF, "A helix scaffold for the assembly of active protein kinases.", Proc Natl Acad Sci U S A, 2008, Vol. 105, Issue 38, 14377-82 [View Abstract] Kannan N, Haste N, Taylor SS, Neuwald AF, "The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis-acting regulatory module.", Proc Natl Acad Sci U S A, 2007, Vol. 104, Issue 4, 1272-7 [View Abstract] Kim C, Cheng CY, Saldanha SA, Taylor SS, "PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.", Cell, 2007, Vol. 130, Issue 6, 1032-43 [View Abstract] Wu J, Brown SH, von Daake S, Taylor SS, "PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity.", Science, 2007, Vol. 318, Issue 5848, 274-9 [View Abstract] Kinderman FS, Kim C, von Daake S, Ma Y, Pham BQ, Spraggon G, Xuong NH, Jennings PA, Taylor SS, "A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase.", Mol Cell, 2006, Vol. 24, Issue 3, 397-408 [View Abstract] Sastri M, Barraclough DM, Carmichael PT, Taylor SS, "A-kinase-interacting protein localizes protein kinase A in the nucleus.", Proc Natl Acad Sci U S A, 2005, Vol. 102, Issue 2, 349-54 [View Abstract] Zhang J, Ma Y, Taylor SS, Tsien RY, "Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering.", Proc Natl Acad Sci U S A, 2001, Vol. 98, Issue 26, 14997-5002 [View Abstract] Wen W, Meinkoth JL, Tsien RY, Taylor SS, "Identification of a signal for rapid export of proteins from the nucleus.", Cell, 1995, Vol. 82, Issue 3, 463-73 [View Abstract] Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM, "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.", Science, 1991, Vol. 253, Issue 5018, 407-14 [View Abstract]