S S Taylor

Summary

Affiliation: University of California
Country: USA

Publications

  1. doi request reprint Pseudokinases from a structural perspective
    Susan S Taylor
    Department of Biomedical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, U S A
    Biochem Soc Trans 41:981-6. 2013
  2. pmc PKA: lessons learned after twenty years
    Susan S Taylor
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0654, USA
    Biochim Biophys Acta 1834:1271-8. 2013
  3. doi request reprint Assembly of allosteric macromolecular switches: lessons from PKA
    Susan S Taylor
    Department of Pharmacology, University of California, San Diego, La Jolla, 92093 90654, USA
    Nat Rev Mol Cell Biol 13:646-58. 2012
  4. pmc Evolution of the eukaryotic protein kinases as dynamic molecular switches
    Susan 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
  5. pmc Evolution of allostery in the cyclic nucleotide binding module
    Natarajan Kannan
    Department of Chemistry and Biochemistry, University of California, Gilman Drive, La Jolla, California 92093 0654, USA
    Genome Biol 8:R264. 2007
  6. ncbi request reprint Protein kinase inhibition: natural and synthetic variations on a theme
    S 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
  7. ncbi request reprint Dynamics of signaling by PKA
    Susan 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
  8. pmc Protein kinases: evolution of dynamic regulatory proteins
    Susan 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
  9. pmc Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug design
    Susan 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
  10. pmc D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain
    L 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

Collaborators

Detail Information

Publications102 found, 100 shown here

  1. doi request reprint Pseudokinases from a structural perspective
    Susan S Taylor
    Department of Biomedical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, U S A
    Biochem Soc Trans 41:981-6. 2013
    ....
  2. pmc PKA: lessons learned after twenty years
    Susan S Taylor
    Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093 0654, USA
    Biochim Biophys Acta 1834:1271-8. 2013
    ..Understanding these dynamic macromolecular complexes is the challenge that we now face. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012)...
  3. doi request reprint Assembly of allosteric macromolecular switches: lessons from PKA
    Susan S Taylor
    Department of Pharmacology, University of California, San Diego, La Jolla, 92093 90654, USA
    Nat Rev Mol Cell Biol 13:646-58. 2012
    ....
  4. pmc Evolution of the eukaryotic protein kinases as dynamic molecular switches
    Susan 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...
  5. pmc Evolution of allostery in the cyclic nucleotide binding module
    Natarajan 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...
  6. ncbi request reprint Protein kinase inhibition: natural and synthetic variations on a theme
    S 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...
  7. ncbi request reprint Dynamics of signaling by PKA
    Susan 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...
  8. pmc Protein kinases: evolution of dynamic regulatory proteins
    Susan 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...
  9. pmc Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug design
    Susan 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...
  10. pmc D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain
    L 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...
  11. ncbi request reprint A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibility
    N 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...
  12. ncbi request reprint Crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MgATP and peptide inhibitor
    J 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...
  13. ncbi request reprint Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of cAMP-dependent protein kinase complexed with the peptide inhibitor PKI(5-24) and adenosine
    N 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...
  14. ncbi request reprint Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
    D 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...
  15. ncbi request reprint cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes
    S S Taylor
    Department of Chemistry, University of California, San Diego, La Jolla 92093
    Annu Rev Biochem 59:971-1005. 1990
    ....
  16. pmc Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein
    L 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...
  17. ncbi request reprint Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains
    Y 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...
  18. ncbi request reprint Dissecting the cooperative reassociation of the regulatory and catalytic subunits of cAMP-dependent protein kinase. Role of Trp-196 in the catalytic subunit
    R 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...
  19. ncbi request reprint Molecular basis for regulatory subunit diversity in cAMP-dependent protein kinase: crystal structure of the type II beta regulatory subunit
    T C Diller
    Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, CA, USA
    Structure 9:73-82. 2001
    ....
  20. ncbi request reprint PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity
    Jian 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...
  21. ncbi request reprint PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation
    Choel 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...
  22. ncbi request reprint PKA: a portrait of protein kinase dynamics
    S 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...
  23. pmc PKA, PKC, and AKAP localization in and around the neuromuscular junction
    G 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...
  24. pmc Global consequences of activation loop phosphorylation on protein kinase A
    Jon M Steichen
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
    J Biol Chem 285:3825-32. 2010
    ....
  25. ncbi request reprint Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1
    Michael 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
    ....
  26. ncbi request reprint Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA
    Choel 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...
  27. ncbi request reprint Differential binding of cAMP-dependent protein kinase regulatory subunit isoforms Ialpha and IIbeta to the catalytic subunit
    X 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...
  28. ncbi request reprint Balanol analogues probe specificity determinants and the conformational malleability of the cyclic 3',5'-adenosine monophosphate-dependent protein kinase catalytic subunit
    Pearl 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...
  29. ncbi request reprint The catalytic subunit of cAMP-dependent protein kinase: prototype for an extended network of communication
    C 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...
  30. pmc NH2-Terminal targeting motifs direct dual specificity A-kinase-anchoring protein 1 (D-AKAP1) to either mitochondria or endoplasmic reticulum
    L 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...
  31. pmc Shc and Enigma are both required for mitogenic signaling by Ret/ptc2
    K 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...
  32. pmc Phosphorylation and activation of cAMP-dependent protein kinase by phosphoinositide-dependent protein kinase
    X 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...
  33. ncbi request reprint cAMP-dependent protein kinase regulatory subunit type IIbeta: active site mutations define an isoform-specific network for allosteric signaling by cAMP
    Kerri 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...
  34. ncbi request reprint RIalpha subunit of PKA: a cAMP-free structure reveals a hydrophobic capping mechanism for docking cAMP into site B
    Jian 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...
  35. ncbi request reprint Catalytic independent functions of a protein kinase as revealed by a kinase-dead mutant: study of the Lys72His mutant of cAMP-dependent kinase
    Ganesh 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
    ....
  36. ncbi request reprint 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...
  37. ncbi request reprint Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A
    H Harada
    Division of Molecular Oncology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Mol Cell 3:413-22. 1999
    ..Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor...
  38. ncbi request reprint Determinants of ligand binding to cAMP-dependent protein kinase
    P H H├╝nenberger
    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...
  39. ncbi request reprint The conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding
    Dominico 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
    ....
  40. pmc Comparative surface geometry of the protein kinase family
    Elaine 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...
  41. ncbi request reprint Amide H/2H exchange reveals communication between the cAMP and catalytic subunit-binding sites in the R(I)alpha subunit of protein kinase A
    Ganesh 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...
  42. pmc Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering
    J 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
    ....
  43. pmc Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix
    Jian 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...
  44. pmc A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase
    Francis 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...
  45. ncbi request reprint Enhanced dephosphorylation of cAMP-dependent protein kinase by oxidation and thiol modification
    Kenneth 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...
  46. ncbi request reprint Cyclic-AMP and pseudosubstrate effects on type-I A-kinase regulatory and catalytic subunit binding kinetics
    Ganesh 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...
  47. ncbi request reprint 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 cA
    Jian 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...
  48. pmc Identification of the protein kinase A regulatory RIalpha-catalytic subunit interface by amide H/2H exchange and protein docking
    Ganesh 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...
  49. ncbi request reprint Dynamic features of cAMP-dependent protein kinase revealed by apoenzyme crystal structure
    Pearl 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
    ....
  50. ncbi request reprint Conformational differences among solution structures of the type Ialpha, IIalpha and IIbeta protein kinase A regulatory subunit homodimers: role of the linker regions
    Dominico 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
    ....
  51. pmc 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...
  52. ncbi request reprint Identification of a novel protein kinase A anchoring protein that binds both type I and type II regulatory subunits
    L 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...
  53. pmc Analogous regulatory sites within the alphaC-beta4 loop regions of ZAP-70 tyrosine kinase and AGC kinases
    Natarajan 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...
  54. pmc 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 spectrometry
    Ganesh 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
    ....
  55. ncbi request reprint Structure and dynamics of PKA signaling proteins
    Choel 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
  56. ncbi request reprint Differential effects of substrate on type I and type II PKA holoenzyme dissociation
    Dominico 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...
  57. pmc A transition path ensemble study reveals a linchpin role for Mg(2+) during rate-limiting ADP release from protein kinase A
    Ilja 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...
  58. pmc Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity
    Ganapathy 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...
  59. ncbi request reprint Isoform-specific PKA dynamics revealed by dye-triggered aggregation and DAKAP1alpha-mediated localization in living cells
    Brent 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...
  60. ncbi request reprint Dynamic binding of PKA regulatory subunit RI alpha
    Justin 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...
  61. pmc A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP
    Dominico Vigil
    Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA 92037, USA
    Protein Sci 15:113-21. 2006
    ....
  62. pmc Distinct interaction modes of an AKAP bound to two regulatory subunit isoforms of protein kinase A revealed by amide hydrogen/deuterium exchange
    Lora 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...
  63. pmc A helix scaffold for the assembly of active protein kinases
    Alexandr 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...
  64. ncbi request reprint Related protein-protein interaction modules present drastically different surface topographies despite a conserved helical platform
    Poopak 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...
  65. pmc A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains
    Alexandr 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...
  66. ncbi request reprint Crystal structure of a cAMP-dependent protein kinase mutant at 1.26A: new insights into the catalytic mechanism
    Jie 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...
  67. ncbi request reprint Endogenous tryptophan residues of cAPK regulatory subunit type IIbeta reveal local variations in environments and dynamics
    Kerri 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...
  68. ncbi request reprint Isoform specific differences in binding of a dual-specificity A-kinase anchoring protein to type I and type II regulatory subunits of PKA
    Lora 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
    ....
  69. pmc Novel isoform-specific interfaces revealed by PKA RIIbeta holoenzyme structures
    Simon 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...
  70. ncbi request reprint Identification of ChChd3 as a novel substrate of the cAMP-dependent protein kinase (PKA) using an analog-sensitive catalytic subunit
    Sharmin 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...
  71. pmc The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of protein kinase C through a conserved PXXP motif in the C-terminal tail
    Christine M Gould
    Pharmacology Department, University of California, San Diego, La Jolla, California 92039 0721, USA
    J Biol Chem 284:4921-35. 2009
    ....
  72. ncbi request reprint Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteins
    Chinten James Lim
    Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
    Nat Cell Biol 9:415-21. 2007
    ....
  73. ncbi request reprint 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...
  74. pmc Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism
    Alexandr 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...
  75. ncbi request reprint Consequences of lysine 72 mutation on the phosphorylation and activation state of cAMP-dependent kinase
    Ganesh 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
    ....
  76. ncbi request reprint Regulation of cAMP-dependent protein kinase activity by glutathionylation
    Kenneth 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...
  77. pmc A-kinase-interacting protein localizes protein kinase A in the nucleus
    Mira 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...
  78. ncbi request reprint Antiparallel alignment of the two protomers of the regulatory subunit dimer of cAMP-dependent protein kinase I
    J 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...
  79. pmc A chimeric mechanism for polyvalent trans-phosphorylation of PKA by PDK1
    Robert 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...
  80. ncbi request reprint 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
    ....
  81. ncbi request reprint Structural basis for peptide binding in protein kinase A. Role of glutamic acid 203 and tyrosine 204 in the peptide-positioning loop
    Michael 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...
  82. ncbi request reprint PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking
    Susan 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...
  83. pmc Dissecting the cAMP-inducible allosteric switch in protein kinase A RIalpha
    Timothy J Sjoberg
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093 0654, USA
    Protein Sci 19:1213-21. 2010
    ....
  84. ncbi request reprint Protein kinase resource: an integrated environment for phosphorylation research
    Roland H Niedner
    San Diego Supercomputer Center, University of California San Diego, La Jolla, California 92093, USA
    Proteins 63:78-86. 2006
    ....
  85. pmc The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways
    Neal 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...
  86. pmc Assay principle for modulators of protein-protein interactions and its application to non-ATP-competitive ligands targeting protein kinase A
    S Adrian Saldanha
    Department of Chemistry and Biochemistry, University of California, La Jolla, California 92093, USA
    Anal Chem 78:8265-72. 2006
    ....
  87. ncbi request reprint Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
    D 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...
  88. ncbi request reprint Cowpea mosaic virus: from the presentation of antigenic peptides to the display of active biomaterials
    A 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...
  89. ncbi request reprint Classification and phylogenetic analysis of the cAMP-dependent protein kinase regulatory subunit family
    Jaume 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...
  90. pmc Designing isoform-specific peptide disruptors of protein kinase A localization
    Lora 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...
  91. pmc Identifying critical non-catalytic residues that modulate protein kinase A activity
    Eileen 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...
  92. ncbi request reprint Solution scattering reveals large differences in the global structures of type II protein kinase A isoforms
    Dominico 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...
  93. ncbi request reprint C subunits binding to the protein kinase A RI alpha dimer induce a large conformational change
    William 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...
  94. ncbi request reprint NMR assignment of the cAMP-binding domain A of the PKA regulatory subunit
    Veronica Esposito
    Department of Chemistry, McMaster University, 1280 Main St W, Hamilton, Ontario, L8S 4M1, Canada
    J Biomol NMR 36:64. 2006
  95. ncbi request reprint Evidence for an internal entropy contribution to phosphoryl transfer: a study of domain closure, backbone flexibility, and the catalytic cycle of cAMP-dependent protein kinase
    Fei 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...
  96. ncbi request reprint Phosphorylation reaction in cAPK protein kinase-free energy quantum mechanical/molecular mechanics simulations
    Marat 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...
  97. ncbi request reprint Conserved spatial patterns across the protein kinase family
    Lynn 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...
  98. pmc Allosteric cooperativity in protein kinase A
    Larry 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...
  99. pmc Congenital disease SNPs target lineage specific structural elements in protein kinases
    Ali 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...
  100. pmc cAMP activation of PKA defines an ancient signaling mechanism
    Rahul 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...
  101. ncbi request reprint PDZK1: II. an anchoring site for the PKA-binding protein D-AKAP2 in renal proximal tubular cells
    Serge 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 Grants56

  1. Protein Kinase Regulatory Subunit 1-Directed Mutagenesis
    Susan Taylor; Fiscal Year: 2005
    ..Mutant forms of RI-alpha and RII-beta will also be characterized. ..
  2. PROTEIN KINASE REGULATORY SUBUNIT 1--DIRECTED MUTAGENES
    Susan 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. ..
  3. Protein Kinase Regulatory 1 - Directed Mutagenesis
    Susan 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. ..
  4. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2011
    ....
  5. Protein Kinase: Primary Structure and cAMP Interactions
    Susan 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. ..
  6. Protein Kinase Regulatory Subunit I Directed Mutagenesis
    Susan 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. ..
  7. Protein Kinase - Primary Structure and cAMP Interaction
    Susan S Taylor; Fiscal Year: 2010
    ....
  8. Protein Kinase Regulatory 1 - Directed Mutagenesis
    Susan 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. ..
  9. MOLECULAR BIOPHYSICS TRAINING PROGRAM
    Susan Taylor; Fiscal Year: 2007
    ..abstract_text> ..
  10. PKA & PKC Targeting Mechanisms
    Susan Taylor; Fiscal Year: 2007
    ....
  11. PROTEIN KINASE REGULATORY SUBUNIT 1--DIRECTED MUTAGENES
    Susan Taylor; Fiscal Year: 1999
    ..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. ..
  12. PROTEIN KINASE--PRIMARY STRUCTURE AND C-AMP INTERACTION
    Susan 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...
  13. PROTEIN KINASE: PRIMARY STRUCTURE AND C-AMP INTERACTION
    Susan Taylor; Fiscal Year: 1980
    ..If suitable crystals are grown, they will be studied by x-ray diffraction in the Crystallography Division of our department. ..
  14. PROTEIN KINASE REGULATORY SUBUNIT I--DIRECTED MUTAGENES
    Susan 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...
  15. PROTEIN KINASE: PRIMARY STRUCTURE AND CAMP INTERACTION
    Susan 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...