Research Topics
Genomes and Genes
| S S TaylorSummaryAffiliation: University of California Country: USA Publications
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Detail Information
Publications
Assembly of allosteric macromolecular switches: lessons from PKASusan S Taylor
Department of Pharmacology, University of California, San Diego, La Jolla, 92093 90654, USA
Nat Rev Mol Cell Biol 13:646-58. 2012....
Evolution of the eukaryotic protein kinases as dynamic molecular switchesSusan S Taylor
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
Philos Trans R Soc Lond B Biol Sci 367:2517-28. 2012..In this way, the cell creates discrete foci that most likely represent the physiological environment for cyclic AMP-mediated signalling...- Evolution of allostery in the cyclic nucleotide binding moduleNatarajan Kannan
Department of Chemistry and Biochemistry, University of California, Gilman Drive, La Jolla, California 92093 0654, USA
Genome Biol 8:R264. 2007..In this study, we analyze the evolutionary information embedded in genomic sequences to explore the diversity of signaling through the CNB domain and also how the CNB domain elicits a cellular response upon binding to cAMP... 
Protein kinase inhibition: natural and synthetic variations on a themeS S Taylor
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093 0654, USA
Curr Opin Chem Biol 1:219-26. 1997..Although targeting of the ATP binding site is proving to be very successful, there is also wide latitude for designing inhibitors that target other surfaces of the kinases...- Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug designSusan S Taylor
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093 0654, USA
Biochim Biophys Acta 1784:16-26. 2008..This targeting mechanism, which localizes PKA near to its protein substrates, is also a target for therapeutic intervention of PKA signaling... - Dynamics of signaling by PKASusan S Taylor
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0654, USA
Biochim Biophys Acta 1754:25-37. 2005..RIalpha is a highly malleable protein. Using small angle X-ray scattering, the overall shape of the regulatory subunits and corresponding holoenzymes have been elucidated. These studies reveal striking and surprising isoform differences... - Protein kinases: evolution of dynamic regulatory proteinsSusan S Taylor
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
Trends Biochem Sci 36:65-77. 2011..Protein kinases thus represent a unique, highly dynamic, and precisely regulated set of switches that control most biological events in eukaryotic cells... - D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domainL J Huang
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, School of Medicine, University of California at San Diego, La Jolla, CA 92093 0654, USA
Proc Natl Acad Sci U S A 94:11184-9. 1997..The presence of this domain raises the intriguing possibility that D-AKAP2 may interact with a Galpha protein thus providing a link between the signaling machinery at the plasma membrane and the downstream kinase... - A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibilityN Narayana
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0359, USA
Structure 5:921-35. 1997..To further understand the conformational changes that occur in different liganded and unliganded states of cAPK, the catalytic subunit of cAPK was crystallized in the absence of peptide inhibitor... - Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitorJ Zheng
Department of Chemistry, University of California, San Diego, La Jolla 92093
Biochemistry 32:2154-61. 1993..Asp166 is positioned to serve as a catalytic base. The structure is correlated with previous chemical evidence, and the features that distinguish this nucleotide binding motif from other nucleotide binding proteins are delineated... - Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of cAMP-dependent protein kinase complexed with the peptide inhibitor PKI(5-24) and adenosineN Narayana
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0654, USA
Biochemistry 36:4438-48. 1997..This glycine-rich loop is thus the most mobile component of the active site cleft, with the tip of the loop being highly sensitive to what occupies the gamma-subsite... - Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinaseD R Knighton
Department of Chemistry, University of California, San Diego, La Jolla 92093 0654
Science 253:414-20. 1991..Amino acids associated with peptide recognition, nonconserved, extend over a large surface area... - cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymesS S Taylor
Department of Chemistry, University of California, San Diego, La Jolla 92093
Annu Rev Biochem 59:971-1005. 1990.... - Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring proteinL Wang
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093 0654, USA
Proc Natl Acad Sci U S A 98:3220-5. 2001..D-AKAP2 from all three species is highly enriched in mitochondria. The mitochondrial localization and the presence of RGS domains in D-AKAP2 may have important implications for its function in PKA and G protein signal transduction... - Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domainsY Su
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0654, USA
Science 269:807-13. 1995..This structure provides a molecular basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase... - Dissecting the cooperative reassociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase. Role of Trp-196 in the catalytic subunitR M Gibson
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 272:31998-2005. 1997..One of these mutants, rR(R333K), having a defect in cAMP binding site B formed a stable complex with rC(W196R) in the absence of cAMP. However, unlike wild-type holoenzyme, this complex was active... - Molecular basis for regulatory subunit diversity in cAMP-dependent protein kinase: crystal structure of the type II beta regulatory subunitT C Diller
Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, CA, USA
Structure 9:73-82. 2001.... - PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activationChoel Kim
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0654, USA
Cell 130:1032-43. 2007..Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP... - PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversityJian Wu
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
Science 318:274-9. 2007..This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA... - PKA, PKC, and AKAP localization in and around the neuromuscular junctionG A Perkins
Department of Neurosciences and the National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093 0608, USA
BMC Neurosci 2:17. 2001..We found previously that a new class of AKAPs, dual-specific AKAPs, denoted D-AKAP1 and D-AKAP2, bind to RIalpha in addition to the RII subunits... - Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1Michael J Moore
Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 277:47878-84. 2002.... - Global consequences of activation loop phosphorylation on protein kinase AJon M Steichen
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
J Biol Chem 285:3825-32. 2010.... - Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKAChoel Kim
Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USA
Science 307:690-6. 2005..The beta barrel of cAMP binding domain A, which is the docking site for cAMP, remains largely intact in the complex, whereas the helical subdomain undergoes major reorganization... - PKA: a portrait of protein kinase dynamicsS S Taylor
Howard Hughes Medical Institute, Bethesda, MD, USA
Biochim Biophys Acta 1697:259-69. 2004..The molecular features of these molecules are described. Finally, we describe a new recombinantly expressed PKA reporter that allows us to monitor PKA activity in living cells... - Differential binding of cAMP-dependent protein kinase regulatory subunit isoforms Ialpha and IIbeta to the catalytic subunitX Cheng
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, California 92093-0654, USA
J Biol Chem 276:4102-8. 2001..These isoform-specific differences would dictate a significantly different domain organization in the type I and type II holoenzymes... - Balanol analogues probe specificity determinants and the conformational malleability of the cyclic 3',5'-adenosine monophosphate-dependent protein kinase catalytic subunitPearl Akamine
Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, School of Medicine, University of California-San Diego, La Jolla, CA 92093, USA
Biochemistry 43:85-96. 2004..By understanding the details of ligand binding, more specific and potent inhibitors may be designed that differentiate among closely related AGC protein kinase family members... - The catalytic subunit of cAMP-dependent protein kinase: prototype for an extended network of communicationC M Smith
San Diego Supercomputer Center, University of California, La Jolla 92093 0505, USA
Prog Biophys Mol Biol 71:313-41. 1999..This review defines key sequence and structural elements, describes what is currently known about the molecular interactions, and how they are involved in catalysis... - NH2-Terminal targeting motifs direct dual specificity A-kinase-anchoring protein 1 (D-AKAP1) to either mitochondria or endoplasmic reticulumL J Huang
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
J Cell Biol 145:951-9. 1999..This represents the first example of a differentially targeted AKAP and adds an additional level of complexity to the PKA signaling network... - Phosphorylation and activation of cAMP-dependent protein kinase by phosphoinositide-dependent protein kinaseX Cheng
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093 0654, USA
Proc Natl Acad Sci U S A 95:9849-54. 1998..PDK1, or one of its homologs, is thus a likely candidate for the in vivo PKA kinase that phosphorylates Thr-197. This finding opens a new dimension in our thinking about this ubiquitous protein kinase and how it is regulated in the cell... - Shc and Enigma are both required for mitogenic signaling by Ret/ptc2K Durick
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0654, USA
Mol Cell Biol 18:2298-308. 1998..Because Shc and Enigma interact with the same site on a Ret/ptc2 monomer, dimerization of Ret/ptc2 allows assembly of molecular complexes that are properly localized via Enigma and transmit mitogenic signals via Shc... - RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site BJian Wu
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
Structure 12:1057-65. 2004..In the absence of cAMP, the "cap" is released via an extension of the C-terminal helix. This simple hinge mechanism for binding and release of cAMP also provides a mechanism for allosteric communication between sites A and B... - Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase- Madhusudan
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
Nat Struct Biol 9:273-7. 2002..This arrangement suggests that aluminum fluoride mimics the transition state and provides the first direct structural evidence for the in-line mechanism of phosphoryl transfer in a protein kinase... - Catalytic independent functions of a protein kinase as revealed by a kinase-dead mutant: study of the Lys72His mutant of cAMP-dependent kinaseGanesh H Iyer
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive 0654, La Jolla, CA 92093-0654, USA
J Mol Biol 351:1110-22. 2005.... - cAMP-dependent protein kinase regulatory subunit type IIbeta: active site mutations define an isoform-specific network for allosteric signaling by cAMPKerri M Zawadzki
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0654, USA
J Biol Chem 279:7029-36. 2004..In RIalpha, removal of the B domain generates a protein that is more difficult to activate than the wild-type protein... - Determinants of ligand binding to cAMP-dependent protein kinaseP H Hünenberger
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla 92093 0365, USA
Biochemistry 38:2358-66. 1999..The disposition of hydrogen-bonding groups in the ligand is therefore crucial for binding specificity. These observations should be valuable guides in the design of potent and specific kinase inhibitors... - Comparative surface geometry of the protein kinase familyElaine E Thompson
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, 92093, USA
Protein Sci 18:2016-26. 2009..Sites identified by this algorithm have revealed structural and spatially conserved features of the kinase family and potential conserved intermolecular and intramolecular binding sites... - Amide H/2H exchange reveals communication between the cAMP and catalytic subunit-binding sites in the R(I)alpha subunit of protein kinase AGanesh S Anand
Howard Hughes Medical Institute, University of California, San Diego 9500 Gilman Drive, La Jolla, CA 92093-0359, USA
J Mol Biol 323:377-86. 2002..These results suggest that the mutually exclusive binding of either cAMP or C-subunit is controlled by binding at one site transmitting long distance changes to the other site... - The conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit bindingDominico Vigil
Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92037, USA
J Biol Chem 280:35521-7. 2005.... - Genetically encoded reporters of protein kinase A activity reveal impact of substrate tetheringJ Zhang
Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 98:14997-5002. 2001.... - Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structurePearl Akamine
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0654, USA
J Mol Biol 327:159-71. 2003.... - Crystal structures of RIalpha subunit of cyclic adenosine 5'-monophosphate (cAMP)-dependent protein kinase complexed with (Rp)-adenosine 3',5'-cyclic monophosphothioate and (Sp)-adenosine 3',5'-cyclic monophosphothioate, the phosphothioate analogues of cAJian Wu
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0654, USA
Biochemistry 43:6620-9. 2004..This strand forms an intermolecular antiparallel beta-sheet with the same strand in an adjacent molecule and implies that the RIalpha subunit can form a weak homodimer even in the absence of its dimerization domain... - Conformational differences among solution structures of the type Ialpha, IIalpha and IIbeta protein kinase A regulatory subunit homodimers: role of the linker regionsDominico Vigil
Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92037, USA
J Mol Biol 337:1183-94. 2004.... - Cyclic-AMP and pseudosubstrate effects on type-I A-kinase regulatory and catalytic subunit binding kineticsGanesh Anand
Department of Chemistry Biochemistry, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92037, USA
Biochemistry 46:9283-91. 2007..Moreover, the ability of the substrate to facilitate cAMP-induced dissociation results from the mass action effect of excess substrate and not from direct substrate binding to holoenzyme... - Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helixJian Wu
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, Leichtag 415, La Jolla, CA 92093, USA
Protein Sci 14:2871-9. 2005..Finally, based on temperature factors, this mutant structure is more stable than the wild-type C-subunit in the apo state... - Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein dockingGanesh S Anand
Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA
Proc Natl Acad Sci U S A 100:13264-9. 2003..This holoenzyme structure satisfies all previous experimental data on the complex and allows prediction of new contacts between the two subunits... - Enhanced dephosphorylation of cAMP-dependent protein kinase by oxidation and thiol modificationKenneth M Humphries
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and Department of Pharmacology, The University of California, San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 280:2750-8. 2005..Our results also demonstrated that NEM treatment of PC12 cells enhanced the dephosphorylation of the protein kinase Calpha activation loop, suggesting a common mechanism of regulation among members of the AGC family of kinases... - Dissecting interdomain communication within cAPK regulatory subunit type IIbeta using enhanced amide hydrogen/deuterium exchange mass spectrometry (DXMS)Kerri M Zawadzki
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA
Protein Sci 12:1980-90. 2003..This interdomain communication appears to be a unidirectional pathway, as mutation of Arg230 in cAB-A does not effect dynamics of the cAB-B domain... - A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinaseFrancis S Kinderman
Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, California 92093, USA
Mol Cell 24:397-408. 2006..RIalpha, with a cavity in the groove, can accept a bulky tryptophan, whereas RIIalpha requires valine... - Identification of a novel protein kinase A anchoring protein that binds both type I and type II regulatory subunitsL J Huang
Department of Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 272:8057-64. 1997..These results raise a novel possibility that the type I regulatory subunit may be anchored via anchoring proteins... - Distinct interaction modes of an AKAP bound to two regulatory subunit isoforms of protein kinase A revealed by amide hydrogen/deuterium exchangeLora L Burns-Hamuro
Department of Medicine, University of California at San Diego, Department 0656, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
Protein Sci 14:2982-92. 2005..DXMS provides valuable structural information for understanding binding specificity in the absence of a high-resolution structure, and can readily be applied to other protein-ligand and protein-protein interactions... - Structure and dynamics of PKA signaling proteinsChoel Kim
Department of Chemistry/Biochemistry, Howard Hughes Medical Institute, University of California, Leichtag Biomedical Research Building, Room 412, 9500 Gilman Dr, La Jolla, CA 92093-0654, USA
Eur J Cell Biol 85:651-4. 2006 - Identification of ChChd3 as a novel substrate of the cAMP-dependent protein kinase (PKA) using an analog-sensitive catalytic subunitSharmin Schauble
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 282:14952-9. 2007..This mutant recombinant C-subunit was used to identify three novel PKA substrates. One protein, a novel mitochondrial ChChd protein, ChChd3, was identified, suggesting that PKA may regulate mitochondria proteins... - Isoform-specific PKA dynamics revealed by dye-triggered aggregation and DAKAP1alpha-mediated localization in living cellsBrent R Martin
Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Chem Biol 14:1031-42. 2007..Overall, effective separation of type I PKA is substrate dependent, whereas type II PKA dissociation relies on autophosphorylation... - R-subunit isoform specificity in protein kinase A: distinct features of protein interfaces in PKA types I and II by amide H/2H exchange mass spectrometryGanesh S Anand
Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0359, USA
J Mol Biol 374:487-99. 2007.... - Analogous regulatory sites within the alphaC-beta4 loop regions of ZAP-70 tyrosine kinase and AGC kinasesNatarajan Kannan
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093 0654, USA
Biochim Biophys Acta 1784:27-32. 2008..Such cis regulation of protein kinase activity may be a feature of other eukaryotic protein kinase families as well... - A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domainsAlexandr P Kornev
San Diego Supercomputer Center, University of California San Diego, La Jolla, California, United States of America
PLoS Comput Biol 4:e1000056. 2008..Catabolite gene activator protein (CAP) represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains... - Novel isoform-specific interfaces revealed by PKA RIIbeta holoenzyme structuresSimon H J Brown
Departments of Chemistry Biochemistry and Pharmacology, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093 0654, USA
J Mol Biol 393:1070-82. 2009..This novel orientation of the linker peptide provides the first clues as to how this region contributes to the unique organization of the RIIbeta holoenzyme... - A transition path ensemble study reveals a linchpin role for Mg(2+) during rate-limiting ADP release from protein kinase AIlja V Khavrutskii
Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093 0365, USA
Biochemistry 48:11532-45. 2009..The results of the present study enhance understanding of Mg(2+)-dependent association of nucleotides with protein kinases... - Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivityGanapathy N Sarma
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, MC 0654, La Jolla, CA 92093, USA
Structure 18:155-66. 2010..Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity... - Dynamic binding of PKA regulatory subunit RI alphaJustin Gullingsrud
Department of Chemistry and Biochemistry, University of California, San Diego, California 92093, USA
Structure 14:141-9. 2006..The model structure is consistent with available experimental data... - A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMPDominico Vigil
Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA 92037, USA
Protein Sci 15:113-21. 2006.... - Differential effects of substrate on type I and type II PKA holoenzyme dissociationDominico Vigil
Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92037, USA
Biochemistry 43:5629-36. 2004..On the basis of these data and other recently published data, we propose a structural model of type I holoenzyme activation by cAMP... - Isoform specific differences in binding of a dual-specificity A-kinase anchoring protein to type I and type II regulatory subunits of PKALora L Burns
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0654, USA
Biochemistry 42:5754-63. 2003.... - Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: new insights into the catalytic mechanismJie Yang
Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
J Mol Biol 336:473-87. 2004..Thus, the P+1 loop is not merely involved in substrate binding; it mediates the communication between substrate and catalytic residues... - Related protein-protein interaction modules present drastically different surface topographies despite a conserved helical platformPoopak Banky
Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093-0359, USA
J Mol Biol 330:1117-29. 2003..RIalpha and RIIalpha D/D interaction modules present drastically differing dimeric topographies, despite a conserved X-type four-helix bundle structure... - A helix scaffold for the assembly of active protein kinasesAlexandr P Kornev
Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 105:14377-82. 2008..Consideration of these discovered structures helps to explain previously inexplicable results... - Endogenous tryptophan residues of cAPK regulatory subunit type IIbeta reveal local variations in environments and dynamicsKerri M Zawadzki
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, USA
Proteins 51:552-61. 2003..The use of endogenous Trp residues presents a non-perturbing method for studying R-subunit subdomain characteristics in addition to providing the first biophysical data on the RIIbeta linker region... - The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of protein kinase C through a conserved PXXP motif in the C-terminal tailChristine M Gould
Pharmacology Department, University of California, San Diego, La Jolla, California 92039 0721, USA
J Biol Chem 284:4921-35. 2009.... - Surface comparison of active and inactive protein kinases identifies a conserved activation mechanismAlexandr P Kornev
San Diego Supercomputer Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 103:17783-8. 2006..It spans the molecule and plays a coordinating role in activated kinases. The spine is disordered in the inactive kinases and can explain how stabilization of the whole molecule is achieved upon phosphorylation... - Regulation of cAMP-dependent protein kinase activity by glutathionylationKenneth M Humphries
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, The University of California, San Diego, La Jolla, California 92093-0654, USA
J Biol Chem 277:43505-11. 2002..Using biotin-cysteine as means for detecting and purifying thiolated cAPK from cells, we were able to show that, under conditions in which cAPK is inactivated by diamide, it is also readily thiolated... - Mapping intersubunit interactions of the regulatory subunit (RIalpha) in the type I holoenzyme of protein kinase A by amide hydrogen/deuterium exchange mass spectrometry (DXMS)Yoshimoto Hamuro
Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0656, USA
J Mol Biol 340:1185-96. 2004..Furthermore, the difference in the protection patterns between RIalpha and the previously studied RIIbeta upon cAMP-binding suggests isoform-specific differences in cAMP-dependent regulation of PKA activity... - Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteinsChinten James Lim
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
Nat Cell Biol 9:415-21. 2007.... - A-kinase-interacting protein localizes protein kinase A in the nucleusMira Sastri
The Howard Hughes Medical Institute and Departments of Chemistry and Biochemistry and Pharmacology, University of California at San Diego, La Jolla, CA 92093 0654, USA
Proc Natl Acad Sci U S A 102:349-54. 2005..Thus, AKIP1 describes a PKA-interacting protein that can contribute to localization by a mechanism that is distinct from A-kinase anchoring proteins that interact with the regulatory subunits... - Consequences of lysine 72 mutation on the phosphorylation and activation state of cAMP-dependent kinaseGanesh H Iyer
Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
J Biol Chem 280:8800-7. 2005.... - Antiparallel alignment of the two protomers of the regulatory subunit dimer of cAMP-dependent protein kinase IJ Bubis
Department of Chemistry, University of California, San Diego, La Jolla 92093
J Biol Chem 262:14961-6. 1987..In all three proteins, a relatively small, nonhomologous, amino-terminal segment of the polypeptide chain is essential for maintaining the dimeric aggregation state... - A chimeric mechanism for polyvalent trans-phosphorylation of PKA by PDK1Robert A Romano
Department of Chemistry, University of California San Diego, La Jolla, California 92093 0654, USA
Protein Sci 18:1486-97. 2009..The highly regulated turn motifs are the most variable part of the AGC C-tail. Elucidating the highly regulated cis and trans functions of the AGC tail is a significant future challenge... - The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathwaysNeal M Alto
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
J Cell Biol 178:1265-78. 2007..Thus, our findings suggest that the EspF-dependent assembly of SNX9 and N-WASP represents a novel form of signaling mimicry used to promote EPEC pathogenesis and gastrointestinal disease... - Dissecting the cAMP-inducible allosteric switch in protein kinase A RIalphaTimothy J Sjoberg
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
Protein Sci 19:1213-21. 2010.... - PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate dockingSusan S Taylor
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093, USA
Cell 122:823-5. 2005..The structures, coupled with mutagenesis analysis, also demonstrate how phosphorylation of the activation loop can allosterically couple two distal regions, the dimerization and substrate recognition interfaces... - Assay principle for modulators of protein-protein interactions and its application to non-ATP-competitive ligands targeting protein kinase AS Adrian Saldanha
Department of Chemistry and Biochemistry, University of California, La Jolla, California 92093, USA
Anal Chem 78:8265-72. 2006.... - Structural basis for peptide binding in protein kinase A. Role of glutamic acid 203 and tyrosine 204 in the peptide-positioning loopMichael J Moore
Howard Hughes Medical Institute, The Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0654, USA
J Biol Chem 278:10613-8. 2003..An aromatic hydrophobic residue is essential for optimal peptide recognition and is conserved throughout the protein kinase family... - Dynamics of cAPK type IIbeta activation revealed by enhanced amide H/2H exchange mass spectrometry (DXMS)Yoshimoto Hamuro
Department of Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, CA 92093-0656, USA
J Mol Biol 327:1065-76. 2003.... - Protein kinase resource: an integrated environment for phosphorylation researchRoland H Niedner
San Diego Supercomputer Center, University of California San Diego, La Jolla, California 92093, USA
Proteins 63:78-86. 2006.... - Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinaseD R Knighton
Department of Chemistry, University of California, San Diego, La Jolla 92093 0654
Science 253:407-14. 1991..Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis... - Cowpea mosaic virus: from the presentation of antigenic peptides to the display of active biomaterialsA Chatterji
Department of Molecular Biology and Center for Integrative Molecular Biosciences, The Scripps Research Institute, La Jolla, CA 92037, USA
Intervirology 45:362-70. 2002..This new approach is also widely applicable for the direct chemical cross-linking of peptides and full-length protein domains to the viral capsid... - Identifying critical non-catalytic residues that modulate protein kinase A activityEileen J Kennedy
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America
PLoS ONE 4:e4746. 2009..Kinase misregulation has been directly linked to a variety of cancers, underscoring the necessity for understanding intramolecular kinase regulation... - Solution scattering reveals large differences in the global structures of type II protein kinase A isoformsDominico Vigil
Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92037, USA
J Mol Biol 357:880-9. 2006..The results provide an important structural foundation for understanding isoform-specific PKA localization and signaling... - Designing isoform-specific peptide disruptors of protein kinase A localizationLora L Burns-Hamuro
Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0654, USA
Proc Natl Acad Sci U S A 100:4072-7. 2003..This array-based analysis also provides a foundation for biophysical analysis of this docking motif... - Classification and phylogenetic analysis of the cAMP-dependent protein kinase regulatory subunit familyJaume M Canaves
Department of Chemistry and Biochemistry, 0654, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0654, USA
J Mol Evol 54:17-29. 2002..Conversely, residues that define subfamilies or domain types are not conserved and are mostly located on the loop that connects alpha-helix B' and beta strand 7... - Congenital disease SNPs target lineage specific structural elements in protein kinasesAli Torkamani
Graduate Program in Biomedical Sciences, University of California, San Diego, CA 92103, USA
Proc Natl Acad Sci U S A 105:9011-6. 2008..This network was recently shown to be absent in distantly related eukaryotic-like kinases, which lack an exaggerated activation loop and, presumably, are not regulated by phosphorylation... - NMR assignment of the cAMP-binding domain A of the PKA regulatory subunitVeronica Esposito
Department of Chemistry, McMaster University, 1280 Main St. W, Hamilton, Ontario, L8S 4M1, Canada
J Biomol NMR 36:64. 2006 - cAMP activation of PKA defines an ancient signaling mechanismRahul Das
Department of Chemistry, Biochemistry, and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, Canada
Proc Natl Acad Sci U S A 104:93-8. 2007..The proposed model defines a signaling mechanism, conserved in every genome, where allosteric binding of a small ligand disrupts a large protein-protein interface... - C subunits binding to the protein kinase A RI alpha dimer induce a large conformational changeWilliam T Heller
Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA
J Biol Chem 279:19084-90. 2004..In this model, the type I alpha holoenzyme forms a flattened V shape with the RI alpha dimerization domain at the point of the V and the cAMP-binding domains of the RI alpha subunits with their bound catalytic subunits at the ends... - Evidence for an internal entropy contribution to phosphoryl transfer: a study of domain closure, backbone flexibility, and the catalytic cycle of cAMP-dependent protein kinaseFei Li
Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA
J Mol Biol 315:459-69. 2002..Because this order-to-disorder transition coincides with the phosphoryl transfer transition, the results suggest the existence of an internal entropy contribution to catalysis... - Conserved spatial patterns across the protein kinase familyLynn F Ten Eyck
Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
Biochim Biophys Acta 1784:238-43. 2008..Detection of such structures by any other method was not possible as the residues which comprise the spine do not form any sequence or 3D motifs in a traditional sense... - Allosteric cooperativity in protein kinase ALarry R Masterson
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
Proc Natl Acad Sci U S A 105:506-11. 2008..Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases... - Phosphorylation reaction in cAPK protein kinase-free energy quantum mechanical/molecular mechanics simulationsMarat Valiev
Molecular Sciences Software Group, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352, USA
J Phys Chem B 111:13455-64. 2007..Lys-168 maintains a hydrogen bond to a transferring phosphoryl group throughout a reaction process. This interaction increases in the product state and contributes to its stabilization... - RET is constitutively activated by novel tandem mutations that alter the active site resulting in multiple endocrine neoplasia type 2BAaron N Cranston
Cancer Research UK Department of Oncology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Cancer Res 66:10179-87. 2006..Our findings have implications both in the clinic and in the successful development of novel kinase-targeted anticancer drugs... - PDZK1: II. an anchoring site for the PKA-binding protein D-AKAP2 in renal proximal tubular cellsSerge M Gisler
Department of Physiology, University of Zurich, Zurich, Switzerland
Kidney Int 64:1746-54. 2003..Among the identified proteins, a C-terminal fragment of the dual-specific A-kinase anchoring protein 2 (D-AKAP2) was obtained by screening PDZ domain 4...
Research Grants
- Protein Kinase Regulatory Subunit 1-Directed MutagenesisSusan Taylor; Fiscal Year: 2005..Mutant forms of RI-alpha and RII-beta will also be characterized. ..
- PROTEIN KINASE REGULATORY SUBUNIT 1--DIRECTED MUTAGENESSusan Taylor; Fiscal Year: 2001..4) One of our highest priorities during the next granting period will be to obtain high resolution crystal structures of the full length RI alpha-subunit and of a holoenzyme complex of C and (delta 1-91)RI. ..
- Protein Kinase Regulatory 1 - Directed MutagenesisSusan Taylor; Fiscal Year: 2007..The work will not only enhance our basic understanding of these molecular switches but will also open the door to the design of new therapeutics capable of interfering with cell signaling. ..
- Protein Kinase - Primary Structure and cAMP InteractionSusan S Taylor; Fiscal Year: 2011....
- Protein Kinase: Primary Structure and cAMP InteractionsSusan Taylor; Fiscal Year: 2009..Finally, we shall continue to use crystallography to obtain high resolution structures of the various conformational states that we define by our biological studies. ..
- Protein Kinase Regulatory Subunit I Directed MutagenesisSusan S Taylor; Fiscal Year: 2010..The work will not only enhance our basic understanding of these molecular switches but will also open the door for the design of new therapeutics capable of interfering with cell signaling. ..
- Protein Kinase - Primary Structure and cAMP InteractionSusan S Taylor; Fiscal Year: 2010....
- Protein Kinase Regulatory 1 - Directed MutagenesisSusan Taylor; Fiscal Year: 2009..Thework willnot only enhance our basic understanding of these molecular switches but will also open the door to the design of new therapeutics capable of interfering with cell signaling. ..
- MOLECULAR BIOPHYSICS TRAINING PROGRAMSusan Taylor; Fiscal Year: 2007..abstract_text> ..
- PKA & PKC Targeting MechanismsSusan Taylor; Fiscal Year: 2007....
- PROTEIN KINASE--PRIMARY STRUCTURE AND C-AMP INTERACTIONSusan Taylor; Fiscal Year: 1990..The induction of neural R(II) in PC12 cells will be followed with neural-specific monoclonal antibodies. Finally, the sequencing of the antigenic domains of RI, R(II) heart, and R(II) brain will be completed...
- PROTEIN KINASE: PRIMARY STRUCTURE AND C-AMP INTERACTIONSusan Taylor; Fiscal Year: 1980..If suitable crystals are grown, they will be studied by x-ray diffraction in the Crystallography Division of our department. ..
- PROTEIN KINASE REGULATORY SUBUNIT I--DIRECTED MUTAGENESSusan Taylor; Fiscal Year: 1992..Mutant R-subunits which show unique phenotypic properties will be overexpressed in cultured cells in an effort to better understand cAMP-mediated functions...
- PROTEIN KINASE: PRIMARY STRUCTURE AND CAMP INTERACTIONSusan Taylor; Fiscal Year: 1993..Superimposed on the above goals is our intention to continue to facilitate the crystallographic studies by providing wild type and mutant proteins in large quantities...