cyclic amp dependent protein kinases

Summary

Summary: A group of enzymes that are dependent on cyclic AMP and catalyze the phosphorylation of serine or threonine residues on proteins.

Top Publications

  1. ncbi Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
    J de Rooij
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, The Netherlands
    Nature 396:474-7. 1998
  2. ncbi Epac proteins: multi-purpose cAMP targets
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Trends Biochem Sci 31:680-6. 2006
  3. ncbi PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Cell 101:365-76. 2000
  4. ncbi TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0
    Ivo Pedruzzi
    Department of Medical Biochemistry, CMU, University of Geneva, 1211 Geneva 4, Switzerland
    Mol Cell 12:1607-13. 2003
  5. ncbi Transcriptional regulation by the phosphorylation-dependent factor CREB
    B Mayr
    Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 2:599-609. 2001
  6. ncbi Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae
    S J Lin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 289:2126-8. 2000
  7. ncbi Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb
    B Wang
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 100:423-34. 2000
  8. ncbi The novel yeast PAS kinase Rim 15 orchestrates G0-associated antioxidant defense mechanisms
    Elisabetta Cameroni
    Department of Microbiology and Molecular Medicine, Centre Medical Universitaire, Univeristy of Geneva, Switzerland
    Cell Cycle 3:462-8. 2004
  9. ncbi A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
    Jorrit M Enserink
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Nat Cell Biol 4:901-6. 2002
  10. ncbi PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability
    Johnny Roosen
    Functional Biology, Katholieke Universiteit Leuven, Kasteelpark Arenberg, B 3001 Leuven Heverlee, Belgium
    Mol Microbiol 55:862-80. 2005

Detail Information

Publications369 found, 100 shown here

  1. ncbi Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP
    J de Rooij
    Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University, The Netherlands
    Nature 396:474-7. 1998
    ..cAMP strongly induces the GEF activity of Epac towards Rap1 both in vivo and in vitro. We conclude that Epac is a GEF for Rap1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP...
  2. ncbi Epac proteins: multi-purpose cAMP targets
    Johannes L Bos
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Trends Biochem Sci 31:680-6. 2006
    ..In most of these processes, cAMP signaling through protein kinase A (PKA) is also involved, stressing the interconnectivity between Epac- and PKA-mediated signaling...
  3. ncbi PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Cell 101:365-76. 2000
    ..6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein, mAKAP. In failing human hearts, RyR2 is PKA hyperphosphorylated, resulting in defective channel function due to increased sensitivity to Ca2+-induced activation...
  4. ncbi TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0
    Ivo Pedruzzi
    Department of Medical Biochemistry, CMU, University of Geneva, 1211 Geneva 4, Switzerland
    Mol Cell 12:1607-13. 2003
    ..Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G(0), a key developmental process in eukaryotic cells...
  5. ncbi Transcriptional regulation by the phosphorylation-dependent factor CREB
    B Mayr
    Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Mol Cell Biol 2:599-609. 2001
    ..CREB is phosphorylated in response to various signals, but how is specificity achieved in these signalling pathways?..
  6. ncbi Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae
    S J Lin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 289:2126-8. 2000
    ..These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD...
  7. ncbi Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb
    B Wang
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell 100:423-34. 2000
    ..The high relative abundance and potency of Gli3 repressor suggest specialization of Gli3 and its products for negative Hedgehog pathway regulation...
  8. ncbi The novel yeast PAS kinase Rim 15 orchestrates G0-associated antioxidant defense mechanisms
    Elisabetta Cameroni
    Department of Microbiology and Molecular Medicine, Centre Medical Universitaire, Univeristy of Geneva, Switzerland
    Cell Cycle 3:462-8. 2004
    ....
  9. ncbi A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
    Jorrit M Enserink
    Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands
    Nat Cell Biol 4:901-6. 2002
    ..Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes...
  10. ncbi PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability
    Johnny Roosen
    Functional Biology, Katholieke Universiteit Leuven, Kasteelpark Arenberg, B 3001 Leuven Heverlee, Belgium
    Mol Microbiol 55:862-80. 2005
    ..This mechanism allows fine-tuning various nutritional responses in yeast cells, allowing them to adapt metabolism and growth appropriately...
  11. ncbi Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation
    Philip J S Stork
    Vollum Institute and the Dept of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97201, USA
    Trends Cell Biol 12:258-66. 2002
    ..Emerging new data suggest that one of these mechanisms might involve the activation of the GTPase Rap1, which can activate or inhibit ERK signaling in a cell-specific manner...
  12. ncbi cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets
    E Butt
    Medizinische Universitatsklinik, Klinische Biochemie und Pathobiochemie, Federal Republic of Germany
    J Biol Chem 269:14509-17. 1994
    ....
  13. ncbi cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension
    Anne E Christensen
    Department of Anatomy and Cell Biology, University of Bergen, 5009 Bergen, Norway
    J Biol Chem 278:35394-402. 2003
    ..We therefore conclude that cAMP-induced neurite outgrowth is mediated by both Epac and cAPK...
  14. ncbi Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae
    J M Thevelein
    Laboratorium voor Moleculaire Celbiologie, Katholieke Universiteit Leuven, Kardinaal Mercierlaan 92, B 3001 Leuven Heverlee, Flanders, Belgium
    Mol Microbiol 33:904-18. 1999
    ..Cln3 appears to play a crucial role in the connection between the availability of certain nutrients and Cdc28 kinase activity, but it remains to be clarified which nutrient-controlled pathways control Cln3 levels...
  15. 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
    ....
  16. pmc Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans
    J A Alspaugh
    Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 21:3179-91. 2001
    ..These findings define a Galpha protein-cAMP-PKA signaling pathway regulating differentiation and virulence of a human fungal pathogen...
  17. ncbi Spinal axon regeneration induced by elevation of cyclic AMP
    Jin Qiu
    Biology Department, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA
    Neuron 34:895-903. 2002
    ..Importantly, DRG injection of db-cAMP results in extensive regeneration of dorsal column axons lesioned 1 week later. These results may be relevant to developing therapies for spinal cord injury...
  18. pmc An anchored PKA and PDE4 complex regulates subplasmalemmal cAMP dynamics
    Debbie Willoughby
    Department of Pharmacology, University of Cambridge, Cambridge, UK
    EMBO J 25:2051-61. 2006
    ..We propose that gravin-associated PDE4D isoforms provide a means to rapidly terminate subplasmalemmal cAMP signals with concomitant effects on localized ion channels or enzyme activities...
  19. pmc Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae
    X Pan
    Departments of Genetics, Pharmacology and Cancer Biology, Microbiology, and Medicine, The Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 19:4874-87. 1999
    ....
  20. ncbi Pharmacological PKA inhibition: all may not be what it seems
    Andrew J Murray
    School of Medical Sciences, College of Life Sciences and Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
    Sci Signal 1:re4. 2008
    ..Here, I summarize the nonspecific effects of these two compounds and compare their actions with those of other PKA inhibitors...
  21. pmc Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9
    Min Wei
    Andrus Gerontology Center, University of Southern California, Los Angeles, California, United States of America
    PLoS Genet 4:e13. 2008
    ..Notably, the anti-aging effect caused by the inactivation of both pathways is much more potent than that caused by CR...
  22. ncbi Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons
    J A Bibb
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
    Nature 402:669-71. 1999
    ..Thus DARPP-32 is a bifunctional signal transduction molecule which, by distinct mechanisms, controls a serine/threonine kinase and a serine/threonine phosphatase...
  23. ncbi Ionotropic and metabotropic receptors, protein kinase A, protein kinase C, and Src contribute to C-fiber-induced ERK activation and cAMP response element-binding protein phosphorylation in dorsal horn neurons, leading to central sensitization
    Yasuhiko Kawasaki
    Pain Research Center, Department of Anesthesiology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 24:8310-21. 2004
    ....
  24. pmc Epac: A new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell
    George G Holz
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA
    Diabetes 53:5-13. 2004
    ..This article summarizes new findings concerning GLP-1 receptor-mediated signal transduction and seeks to define the relative importance of Epac and PKA to beta-cell stimulus-secretion coupling...
  25. ncbi Specificity in the cAMP/PKA signaling pathway. Differential expression,regulation, and subcellular localization of subunits of PKA
    B S Skalhegg
    Institute for Nutrition Reserarch, University of Oslo, Norway
    Front Biosci 5:D678-93. 2000
    ..Here we will describe features of this signaling pathway that may contribute to explain how differential effects of cAMP may be contributed to features of the PKA signaling pathway...
  26. ncbi Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity
    P Calabresi
    Clinica Neurologica, Dipartimento di Neuroscienze, Universita di Tor Vergata, Rome, Italy
    J Neurosci 20:8443-51. 2000
    ..These kinases appear to be stimulated by the activation of D1-like receptors in distinct neuronal populations...
  27. ncbi Prostaglandin E2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1
    Yasuhiro Kobayashi
    Institute for Oral Science, Matsumoto Dental University, Shiojiri, Nagano, Japan
    J Biol Chem 280:11395-403. 2005
    ..These results suggest that the phosphorylation of the Ser412 residue in TAK1 by PKA is essential for cAMP/PKA-induced up-regulation of osteoclastic differentiation and cytokine production in the precursor cells...
  28. pmc ACTH inhibits bTREK-1 K+ channels through multiple cAMP-dependent signaling pathways
    Haiyan Liu
    Department of Neuroscience, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA
    J Gen Physiol 132:279-94. 2008
    ..The convergent inhibition of bTREK-1 through parallel PKA- and Epac-dependent mechanisms may provide for failsafe membrane depolarization by ACTH...
  29. ncbi Insights into the phosphoryl-transfer mechanism of cAMP-dependent protein kinase from quantum chemical calculations and molecular dynamics simulations
    Natalia Diaz
    Laboratoire de Dynamique Moleculaire, Institut de Biologie Structurale Jean Pierre Ebel, CEA CNRS, 41, rue Jules Horowitz, F 38027 Grenoble Cedex 1, France
    J Am Chem Soc 126:529-42. 2004
    ....
  30. pmc Gating of CFTR by the STAS domain of SLC26 transporters
    Shigeru B H Ko
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9040, USA
    Nat Cell Biol 6:343-50. 2004
    ..These findings provide a new understanding of epithelial chloride and bicarbonate transport and may have important implications for both cystic fibrosis and diseases associated with SLC26T...
  31. pmc Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis
    Xinde Zheng
    Institute of Molecular and Cell Biology, Singapore, Singapore
    EMBO J 23:1845-56. 2004
    ..C. albicans seems to have adapted a conserved strategy to control specifically hyphal morphogenesis...
  32. ncbi Regulation of the exocytotic machinery by cAMP-dependent protein kinase: implications for presynaptic plasticity
    G J O Evans
    Physiological Laboratory, Department of Physiology, Crown St, University of Liverpool, Liverpool L69 3BX, UK
    Biochem Soc Trans 31:824-7. 2003
    ..We also discuss how the function of CSP and Snapin phosphorylation might fit into an interesting aspect of the PKA-dependent enhancement of exocytosis: presynaptic plasticity in the brain...
  33. ncbi Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms
    Kai Soo Tan
    The Comprehensive Center for Inflammatory Disorders, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA
    Cell Signal 19:251-60. 2007
    ....
  34. ncbi Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein alpha in cyclic AMP response element-mediated transcription
    Gerald Thiel
    Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany
    J Neurochem 92:321-36. 2005
    ..Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up-regulate transcription of genes containing CRE motifs in their regulatory regions...
  35. ncbi Negative feedback exerted by cAMP-dependent protein kinase and cAMP phosphodiesterase on subsarcolemmal cAMP signals in intact cardiac myocytes: an in vivo study using adenovirus-mediated expression of CNG channels
    Francesca Rochais
    Laboratoire de Cardiologie Cellulaire et Moleculaire, INSERM U 446, Universite Paris Sud, Faculte de Pharmacie, F 92296 Chatenay Malabry, France
    J Biol Chem 279:52095-105. 2004
    ..This study demonstrates that subsarcolemmal cAMP levels are dynamically regulated by a negative feedback involving PKA stimulation of subsarcolemmal cAMP-PDE...
  36. ncbi Phosphorylation by cAMP-dependent protein kinase is essential for synapsin-induced enhancement of neurotransmitter release in invertebrate neurons
    Ferdinando Fiumara
    Department of Neuroscience, Section of Physiology, University of Torino, Corso Raffaello 30, 10125, Italy
    J Cell Sci 117:5145-54. 2004
    ....
  37. pmc Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence
    Wei Zhao
    Department of Pathology and Laboratory Medicine, University of Cincinnati, P O Box 670529, Cincinnati, Ohio 45267 0529, USA
    Infect Immun 74:4865-74. 2006
    ..Unregulated PKA signaling is detrimental to the virulence of A. fumigatus, perhaps through the reduced susceptibility of the mutant to damage by oxidizing agents and reduced growth kinetics...
  38. ncbi The gene encoding the C gamma catalytic subunit of cAMP-dependent protein kinase is a transcribed retroposon
    N Reinton
    Institute of Medical Biochemistry, University of Oslo, Norway
    Genomics 49:290-7. 1998
    ..Our results indicate that the C gamma gene is a retroposon specifically transcribed in primate testicular germ cells...
  39. ncbi Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells
    Theresa D'Souza
    Laboratory of Cellular and Molecular Biology, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 280:26233-40. 2005
    ..In addition, our findings may have general implications for the regulation of TJs in normal epithelial cells...
  40. doi Cyclic nucleotide analogs as probes of signaling pathways
    Heiko Poppe
    Nat Methods 5:277-8. 2008
  41. ncbi Two novel brain-specific splice variants of the murine Cbeta gene of cAMP-dependent protein kinase
    C R Guthrie
    Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 272:29560-5. 1997
    ..The discrete expression of Cbeta variants in the brain suggests specific functional roles in neuronal signaling...
  42. ncbi Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex
    M Colledge
    Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland 97201, USA
    Neuron 27:107-19. 2000
    ..As AMPA receptor phosphorylation is implicated in regulating synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be centrally involved...
  43. pmc Amplification of dopaminergic signaling by a positive feedback loop
    A Nishi
    Department of Physiology, Kurume University School of Medicine, 67 Asahi Machi, Kurume, Fukuoka 830 0011, Japan
    Proc Natl Acad Sci U S A 97:12840-5. 2000
    ..Together, these results indicate that via positive feedback mechanisms, Cdk5 signaling and PKA signaling are mutually antagonistic...
  44. ncbi Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA receptors: distinct roles of calcineurin and protein phosphatase-2A
    Akinori Nishi
    Department of Physiology, Kurume University School of Medicine, 67 Asahi Machi, Kurume, Fukuoka 830 0011, Japan
    J Neurochem 81:832-41. 2002
    ..The results provide support for a complex effect of glutamate on dopaminergic signaling through the regulation of dephosphorylation of different sites of DARPP-32 by different protein phosphatases...
  45. pmc Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex
    Valeria Wanke
    Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland
    EMBO J 24:4271-8. 2005
    ..Importantly, we also show that Pho80-Pho85 and TORC1 converge on a single amino acid in Rim15. Thus, Rim15 plays a key role in G0 entry through its ability to integrate signaling from the PKA, TORC1, and Pho80-Pho85 pathways...
  46. ncbi Ammonium permease-based sensing mechanism for rapid ammonium activation of the protein kinase A pathway in yeast
    An Van Nuland
    Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 31, B 3001 Leuven Heverlee, Flanders, Belgium
    Mol Microbiol 59:1485-505. 2006
    ..We also show that Mep permease involvement in PKA control is different from their role in haploid invasive growth, in which Mep1 sustains and Mep2 inhibits, in a way independent of the ammonium level in the medium...
  47. pmc Phosphorylation of Gli2 by protein kinase A is required for Gli2 processing and degradation and the Sonic Hedgehog-regulated mouse development
    Yong Pan
    Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, W404, New York, NY 10065, USA
    Dev Biol 326:177-89. 2009
    ..Together, these results indicate that phosphorylation of Gli2 by PKA induces Gli2 processing and destabilization in vivo and plays an important role in the Hh-regulated mouse embryonic patterning...
  48. ncbi Regulation, localization, and anchoring of protein kinase A subunits during mouse sperm capacitation
    P E Visconti
    Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia 19104 6080, USA
    Dev Biol 192:351-63. 1997
    ....
  49. pmc An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase
    Yelena V Budovskaya
    Department of Molecular Genetics, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 102:13933-8. 2005
    ..Moreover, these data show how this approach could be generally used to identify the physiologically relevant occurrences of any protein motif identified in a eukaryotic proteome...
  50. ncbi 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...
  51. ncbi A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose
    L Kraakman
    Laboratorium voor Moleculaire Celbiologie, Katholieke Universiteit Leuven, Institute of Botany and Microbiology
    Mol Microbiol 32:1002-12. 1999
    ..This appears to be the first example of a GPCR system activated by a nutrient in eukaryotic cells. Hence, a subfamily of GPCRs might be involved in nutrient sensing...
  52. ncbi High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224 6825, USA
    Circ Res 98:505-14. 2006
    ....
  53. ncbi Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase
    Durga Prasanna Mohapatra
    Department of Anesthesiology, Friedrich Alexander University Erlangen Nuremberg, 91054 Erlangen, Germany
    J Biol Chem 280:13424-32. 2005
    ..We conclude that Ca2+-dependent desensitization of TRPV1 might be in part regulated through channel dephosphorylation by calcineurin and channel phosphorylation by PKA possibly involving Thr370 as a key amino acid residue...
  54. ncbi Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development
    W Li
    Department of Biological Sciences, Columbia University, New York, New York 10027
    Cell 80:553-62. 1995
    ..PKA therefore appears to be an integral component of the mechanism by which hh regulates the expression of key patterning molecules in imaginal discs...
  55. pmc G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans
    Chaoyang Xue
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Mol Biol Cell 17:667-79. 2006
    ..Activation of the cAMP-PKA pathway by glucose and amino acids represents a nutrient coincidence detection system shared in other pathogenic fungi...
  56. pmc Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein
    Jiuyong Xie
    Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095 1662, USA
    Proc Natl Acad Sci U S A 100:8776-81. 2003
    ..Thus, direct PKA phosphorylation of PTB at Ser-16 modulates the nucleo-cytoplasmic distribution of PTB. This phosphorylation likely plays a role in the cytoplasmic function of PTB...
  57. ncbi Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity
    Diego Centonze
    Clinica Neurologica, Dipartimento di Neuroscienze, Universita di Tor Vergata, 00133 Rome, Italy
    J Neurosci 23:8506-12. 2003
    ....
  58. ncbi Depletion of type IA regulatory subunit (RIalpha) of protein kinase A (PKA) in mammalian cells and tissues activates mTOR and causes autophagic deficiency
    Manos Mavrakis
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Mol Genet 15:2962-71. 2006
    ..These data suggest that RIalpha deficiency decreases autophagy by the activation of mTOR, providing a molecular basis to autophagic deficiency in PPNAD...
  59. ncbi Identification and characterization of novel PKA holoenzymes in human T lymphocytes
    Sigurd Orstavik
    Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway
    FEBS J 272:1559-67. 2005
    ..Our results demonstrate for the first time that various C subunits may colocate on the same PKA holoenzyme to form novel cAMP-responsive enzymes that may mediate specific effects of cAMP...
  60. pmc Epac and PKA: a tale of two intracellular cAMP receptors
    Xiaodong Cheng
    Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    Acta Biochim Biophys Sin (Shanghai) 40:651-62. 2008
    ....
  61. pmc beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi
    George S Baillie
    Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute for Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    Proc Natl Acad Sci U S A 100:940-5. 2003
    ..Thus, receptor-stimulated beta-arrestin-mediated recruitment of PDE4 plays a central role in the regulation of G protein switching by the beta(2)AR in a physiological system, the cardiac myocyte...
  62. ncbi Activation of cAMP response element-mediated gene expression by regulated nuclear transport of TORC proteins
    Mark A Bittinger
    Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA
    Curr Biol 14:2156-61. 2004
    ..Drosophila TORC was also shown to translocate in response to calcineurin activation in vivo. Thus, TORC nuclear translocation is an essential, conserved step in activation of cAMP-responsive genes...
  63. ncbi Cloning and characterization of a novel A-kinase anchoring protein. AKAP 220, association with testicular peroxisomes
    L B Lester
    Vollum Institute, Portland, Oregon 97201, USA
    J Biol Chem 271:9460-5. 1996
    ..Collectively, these results suggest that AKAP 220 may play a role in targeting type II PKA for cAMP-responsive peroxisomal events...
  64. ncbi Regulation of neuronal PKA signaling through AKAP targeting dynamics
    MARK L DELL'ACQUA
    Department of Pharmacology, University of Colorado at Denver and Health Sciences Center at Fitzsimons, P O Box 6511, Mail Stop 8303, Aurora, CO 80045 0508, USA
    Eur J Cell Biol 85:627-33. 2006
    ....
  65. ncbi Oxidant-induced activation of type I protein kinase A is mediated by RI subunit interprotein disulfide bond formation
    Jonathan P Brennan
    Department of Cardiology, King s College London, The Rayne Institute, St Thomas Hospital, London, SE1 7EH United Kingdom
    J Biol Chem 281:21827-36. 2006
    ..In essence, type I PKA contains protein thiols that operate as redox sensors, and their oxidation by hydrogen peroxide directly activates the kinase...
  66. ncbi Activation state of the Ras2 protein and glucose-induced signaling in Saccharomyces cerevisiae
    Sonia Colombo
    Dipartimento di Biotecnologie e Bioscienze, Universita Milano Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
    J Biol Chem 279:46715-22. 2004
    ..Strains with reduced feedback inhibition on cAMP synthesis also display elevated basal and induced Ras2 GTP loading consistent with the Ras2 protein acting as a target of the feedback-inhibition mechanism...
  67. pmc Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation
    Xuewen Pan
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:3981-93. 2002
    ..Our studies illustrate in molecular detail how protein kinase A combinatorially effects a key developmental switch. Similar mechanisms may operate in pathogenic fungi and more complex multicellular eukaryotic organisms...
  68. ncbi Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase
    B J McDonald
    MRC Laboratory for Molecular Cell Biology, University College, London, UK
    Nat Neurosci 1:23-8. 1998
    ..Differential regulation by PKA of postsynaptic GABAA receptors containing different beta subunits may have profound effects on neuronal excitability...
  69. pmc The cAMP binding protein Epac modulates Ca2+ sparks by a Ca2+/calmodulin kinase signalling pathway in rat cardiac myocytes
    Laetitia Pereira
    Inserm U637, Physiopathologie Cardiovasculaire, Montpellier, France
    J Physiol 583:685-94. 2007
    ..Accordingly, we found that Epac increased RyR phosphorylation at the CaMKII site. Altogether, our data reveal a new signalling pathway by which cAMP governs Ca(2+) release and signalling in cardiac myocytes...
  70. ncbi PKA inhibits RhoA activation: a protection mechanism against endothelial barrier dysfunction
    Jing Qiao
    Department of Pharmacology, Rush Presbyterian St Luke s Medical Center, Chicago, Illinois 60612, USA
    Am J Physiol Lung Cell Mol Physiol 284:L972-80. 2003
    ..In conclusion, the results provide evidence that PKA inhibited RhoA activation in endothelial cells, supporting a signaling mechanism of protection against vascular endothelial barrier dysfunction...
  71. pmc EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation
    Elaine Huston
    Neuroscience and Molecular Pharmacology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Proc Natl Acad Sci U S A 105:12791-6. 2008
    ..Through this signaling system EPAC activation can thereby impact on the Ser-473 phosphorylation status of PKB/Akt and the repair of etoposide-induced DSBs...
  72. ncbi Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C
    T J Kamp
    Department of Medicine, University of Wisconsin, Madison, WI 53792 3248, USA
    Circ Res 87:1095-102. 2000
    ..Crosstalk between PKA and PKC pathways occurs in the modulation of I:(Ca). Ultimately, precise regulation of I:(Ca) is needed for normal cardiac function, and alterations in these regulatory pathways may prove important in heart disease...
  73. ncbi PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity
    Jose A Esteban
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Neurosci 6:136-43. 2003
    ..Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity...
  74. ncbi cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits
    T Gao
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Neuron 19:185-96. 1997
    ..Thus, the PKA-mediated regulation of L-type Ca2+ channels is critically dependent on a functional AKAP and phosphorylation of the alpha1C subunit at Ser1928...
  75. ncbi cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity
    Icksoo Lee
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, 540 E Canfield Ave, Detroit, MI 48201, USA
    J Biol Chem 280:6094-100. 2005
    ..At therapeutic concentrations used for asthma relief, theophylline causes lung COX inhibition and decreases cellular ATP levels, suggesting a mechanism for its clinical action...
  76. ncbi cAMP-dependent protein kinase type I regulates ethanol-induced cAMP response element-mediated gene expression via activation of CREB-binding protein and inhibition of MAPK
    Anastasia Constantinescu
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA 94608, USA
    J Biol Chem 279:43321-9. 2004
    ..Under these conditions p90RSK is no longer bound to CBP, thereby promoting CBP-dependent CREB-mediated gene expression...
  77. ncbi Decreased expression of cyclic adenosine monophosphate-regulated aldose reductase (AKR1B1) is associated with malignancy in human sporadic adrenocortical tumors
    Anne Marie Lefrançois-Martinez
    Unité Mixte de Recherche 6547 CNRS Université Blaise Pascal Clermont II, Génétique des Eucaryotes et Endocrinologie Moléculaire, Complexe Universitaire des Cézeaux, 63177 Aubiere, France
    J Clin Endocrinol Metab 89:3010-9. 2004
    ..This might take part in adrenal tumorigenesis and could be investigated as a marker of malignancy for the diagnosis of adrenal tumors...
  78. ncbi PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis
    Susumu Seino
    Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Physiol Rev 85:1303-42. 2005
    ..Localization of cAMP within intracellular compartments (cAMP compartmentation or compartmentalization) may be a key mechanism underlying the distinct effects of cAMP in different domains of the cell...
  79. ncbi Phosphorylated CREB binds specifically to the nuclear protein CBP
    J C Chrivia
    Vollum Institute, Oregon Health Sciences University, Portland 97201
    Nature 365:855-9. 1993
    ..We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB...
  80. pmc Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity
    W Görner
    Vienna Biocenter, Institut für Biochemie und Molekulare Zellbiologie der Universität Wien and Ludwig Boltzmann Forschungsstelle für Biochemie, A 1030 Wien, Austria
    Genes Dev 12:586-97. 1998
    ..We propose stress and cAMP-regulated intracellular localization of Msn2p to be a key step in STRE-dependent transcription and in the general stress response...
  81. pmc mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module
    K L Dodge
    Howard Hughes Medical Institute and Vollum Institute, and Department of Pediatrics, Oregon Health Sciences University, Portland, OR 97201 3098, USA
    EMBO J 20:1921-30. 2001
    ..Disruption of PKA- mAKAP interaction prevents this enhancement of PDE4D3 activity, suggesting that the proximity of both enzymes in the mAKAP signaling complex forms a negative feedback loop to restore basal cAMP levels...
  82. ncbi Regulation of actin-based cell migration by cAMP/PKA
    Alan K Howe
    Department of Pharmacology, Vermont Cancer Center, University of Vermont, HSRF 322, Burlington 05405 0075, USA
    Biochim Biophys Acta 1692:159-74. 2004
    ..This review discusses the growing literature that supports the hypothesis that PKA plays a central role in cytoskeletal regulation and cell migration...
  83. pmc Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons
    Katrin Schnizler
    Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
    J Neurosci 28:4904-17. 2008
    ..Together, these data suggest that PKA anchoring by AKAP150 is essential for the enhancement of TRPV1 function by activation of the PGE(2)/PKA signaling pathway...
  84. ncbi Seven-transmembrane-spanning receptors and heart function
    Howard A Rockman
    Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 415:206-12. 2002
    ..Most of these discoveries have focused on the most common type of cardiac receptor - the seven-transmembrane-spanning receptor or G-protein-coupled receptor...
  85. ncbi Molecular mechanisms of insulin-like growth factor-I mediated regulation of the steroidogenic acute regulatory protein in mouse leydig cells
    Pulak R Manna
    Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA
    Mol Endocrinol 20:362-78. 2006
    ..Collectively, the present studies identify molecular events in IGF-I signaling that may influence testicular growth, development, and the Leydig cell steroidogenic machinery through autocrine/paracrine regulation...
  86. ncbi Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex
    L S Kirschner
    Unit on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA
    Nat Genet 26:89-92. 2000
    ..We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease...
  87. ncbi Crystal structure of an inactive Akt2 kinase domain
    Xin Huang
    Amgen Cambridge Research Center, One Kendall Square, Building 1000, Cambridge, MA 02139, USA
    Structure 11:21-30. 2003
    ..Residues within the linker region between the N- and C-terminal lobes also contribute to the inactive conformation by partially occupying the ATP binding site...
  88. pmc Quantification of dynamic protein complexes using Renilla luciferase fragment complementation applied to protein kinase A activities in vivo
    E Stefan
    Département de Biochimie and Institute for Research in Immunology and Cancer, Universite de Montreal, Succursale Centre Ville, Montreal, QC, Canada
    Proc Natl Acad Sci U S A 104:16916-21. 2007
    ....
  89. pmc Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex
    Dario Diviani
    Département de Pharmacologie et de Toxicologie, Faculte de Medecine, Lausanne, Switzerland
    EMBO J 23:2811-20. 2004
    ..Therefore, while it is known that AKAP-Lbc activity can be stimulated by Galpha12, in this study we demonstrated that it is inhibited by the anchoring of both PKA and 14-3-3...
  90. ncbi MSI1 suppresses hyperactive RAS via the cAMP-dependent protein kinase and independently of chromatin assembly factor-1
    X Zhu
    Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Curr Genet 38:60-70. 2000
    ..MSI1 appears to provide two distinct roles in chromatin modeling as a component of yCAF-1, and in the inhibition of RAS signaling by modulating PKA...
  91. pmc A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes
    M G Newlon
    The Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0359, USA
    EMBO J 20:1651-62. 2001
    ..In a departure from the dimer-dimer interactions seen in other X-type four-helix bundle dimeric proteins, our structures reveal a novel hydrophobic groove that accommodates one AKAP per RIIalpha D/D...
  92. ncbi Structural kinetics of cardiac troponin C mutants linked to familial hypertrophic and dilated cardiomyopathy in troponin complexes
    Wen Ji Dong
    School of Chemical Engineering and Bioengineering, Washington State University, Pullman 99164, USA
    J Biol Chem 283:3424-32. 2008
    ..Both mutations appear to be antagonistic toward phosphorylation signaling between cTnI and cTnC...
  93. pmc Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes
    Rasmus Koefoed Petersen
    BioLigands, International Science Park Odense, DK 5230 Odense M, Denmark
    Mol Cell Biol 28:3804-16. 2008
    ....
  94. ncbi Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes
    Manuela Zaccolo
    Department of Biomedical Sciences and Venetian Institute for Molecular Medicine, University of Padua, Via Orus 2, 35129 Padua, Italy
    Science 295:1711-5. 2002
    ..Furthermore, we demonstrate that such gradients of cAMP specifically activate a subset of protein kinase A molecules anchored in proximity to the T tubule...
  95. ncbi AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation
    D Diviani
    Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA
    J Biol Chem 276:44247-57. 2001
    ..Furthermore, biochemical studies indicate that AKAP-Lbc functions as an adaptor protein to selectively couple Galpha(12) to Rho. Thus, AKAP-Lbc anchors PKA and nucleates the assembly of a Rho-mediated signaling pathway...
  96. pmc The pkaB gene encoding the secondary protein kinase A catalytic subunit has a synthetic lethal interaction with pkaA and plays overlapping and opposite roles in Aspergillus nidulans
    Min Ni
    Department of Food Microbiology and Toxicology, Food Research Institute, University of Wisconsin, Madison, WI 53706, USA
    Eukaryot Cell 4:1465-76. 2005
    ..nidulans...
  97. pmc The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones
    W Huang
    Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 98:160-5. 2001
    ....
  98. ncbi Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections
    Marie K Hoeger-Bement
    Graduate Program in Physical Therapy and Rehabilitation Science, Neuroscience Graduate Program, Pain Research Program, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurosci 23:5437-45. 2003
    ..The mechanical hyperalgesia and phosphorylation of CREB depend on early activation of the cAMP pathway during the first 24 hr but are independent of the cAMP pathway by 1 week after intramuscular injection of acid...
  99. ncbi Increased activation of protein kinase A type I contributes to the T cell deficiency in common variable immunodeficiency
    P Aukrust
    Research Institute for Internal Medicine, Medical Department A, Rikshospitalet, Oslo, Norway
    J Immunol 162:1178-85. 1999
    ....
  100. ncbi A family of cAMP-binding proteins that directly activate Rap1
    H Kawasaki
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, MA, 02139, USA
    Science 282:2275-9. 1998
    ..Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling...
  101. ncbi A novel isoform of human cyclic 3',5'-adenosine monophosphate-dependent protein kinase, c alpha-s, localizes to sperm midpiece
    N Reinton
    Institute of Medical Biochemistry, University of Oslo, N 0317 Oslo, Norway
    Biol Reprod 63:607-11. 2000
    ..This novel C alpha-s splice variant appeared to have an independent anchor in the human sperm midpiece as it could not be completely solubilized even in the presence of both detergent and cAMP...

Research Grants63

  1. Regulation of AKAP79 Postsynaptic Membrane Targeting
    MARK L DELL'ACQUA; Fiscal Year: 2012
    ....
  2. AKAP Regulation of PKA Targeting in the Heart
    Meredith Bond; Fiscal Year: 2009
    ..Our project investigates a novel nuclear AKAP protein, Chd8 that may participate in regulation of cardiac remodeling during ischemic heart failure. ..
  3. VOLTAGE SENSITIVE SODIUM CHANNELS IN BRAIN
    William A Catterall; Fiscal Year: 2013
    ..This basic science information will be essential to understand and treat periodic paralysis, epilepsy, chronic pain, and cardiac arrhythmia. ..
  4. Beta-adrenergic regulation of adipose tissue function by PKA and MAP kinases
    Sheila Collins; Fiscal Year: 2009
    ..PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page ..
  5. Inhibition of GRK2 to Prevent Ventricular Remodeling and Heart Failure After CABG
    Shahab A Akhter; Fiscal Year: 2013
    ..Inhibition of GRK2 activity has important therapeutic promise in this disease process and may represent a novel adjunctive therapy at the time of CABG. ..
  6. Modulation of beta-cell PKA activity affects glucose homeostasis
    Barton Wicksteed; Fiscal Year: 2013
    ..It will also reveal potential pitfalls of harnessing this pathway for the treatment of diabetes. ..
  7. The regulation and function of cytoplasmic foci in quiescent cells
    Paul K Herman; Fiscal Year: 2013
    ..The specific aims of this proposal are: (1) to determine the role of PKA signaling in the regulation of P-body foci formation;and (2) to determine the physiological role of P-body foci in quiescent cells. ..
  8. Eicosanoid Balance in Lung Transplant Injury and Repair
    David Pinsky; Fiscal Year: 2009
    ..This grant seeks to understand the balance between these injurious and protective substances, to develop strategies which may tip the balance in favor of protecting transplanted lungs from lethal injury. ..
  9. Regulation of Cardiac Calcium Channels by an Autoinhibitory Signalling Complex
    William A Catterall; Fiscal Year: 2013
    ..These studies will increase understanding of regulation of the heart by the sympathetic nervous system and give essential new insight into the molecular and functional changes in the Cav1.2 signaling complex in heart failure. ..
  10. Control of Oocyte Maturation in C. elegans
    DAVID IRWIN GREENSTEIN; Fiscal Year: 2013
    ..The small roundworm C. elegans is an established model for studying the hormonal control of meiosis. These studies will define the signaling mechanisms controlling female meiosis and provide insights into the origin of meiotic errors. ..
  11. Sox9-mediated control of chondrogenesis
    VERONIQUE M LEFEBVRE; Fiscal Year: 2013
    ..This knowledge will provide novel insights into mechanisms underlying cartilage malformation and degeneration diseases and will help find suitable treatments. ..
  12. Novel multivalent/multifunctional agents derived from a humanized anti-insulin-li
    Thomas M Cardillo; Fiscal Year: 2010
    ....
  13. The Role of Phosphorylation in Photoreceptor Cell Biology
    ELLEN RUTH WEISS; Fiscal Year: 2010
    ..It is anticipated that these studies will lead to a better understanding of cone function advance our ability to prevent cone-related diseases. ..
  14. Cytoskeletal regulation of endothelial barrier function by WAVE2
    Sunil K Shaw; Fiscal Year: 2010
    ....
  15. Counteracting microbial immune evasion for the treatment of periodontitis
    MEGAN LAVONNE MCINTOSH; Fiscal Year: 2012
    ..This work is expected to help propel development of prophylactic and post-infection treatments which could drastically improve the quality of life of periodontal patients. ..
  16. AKAP Regulation of Neuronal L-type Calcium Channel Signaling to the Nucleus
    MARK L DELL'ACQUA; Fiscal Year: 2013
    ....
  17. Protein Kinase Regulatory Subunit I Directed Mutagenesis
    Susan S Taylor; Fiscal Year: 2013
    ..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. ..
  18. Duplin: A Novel A-Kinase Anchoring Protein
    MAUREEN E O apos DONNELL; Fiscal Year: 2010
    ..This study will test the hypothesis that the nuclear protein duplin/Chd8 mediates PKA-dependent regulation of STATS, exploring a potential mechanism by which STATS regulation could go awry in the failing heart. ..
  19. FSH-STIMULATED SIGNALS THAT REGULATE FOLLICULAR MATURATION
    John H Nilson; Fiscal Year: 2013
    ..Understanding how FSH signals to direct follicular maturation can translate into safer and more effective treatments of infertility and early pregnancy loss as well as new approaches for contraceptive drugs. ..
  20. Protective role of ANP in the models of acute lung injury
    Anna Birukova; Fiscal Year: 2013
    ..We believe that these studies may identify novel protein targets and propose new therapies for prevention of pulmonary vascular barrier dysfunction associated with acute lung inflammation and injury. ..
  21. New Insights into Motor Neuron Disease
    John K Fink; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: This project will advance our knowledge of the molecular basis and ultimately treatments for motor neuron diseases including amyotrophic lateral sclerosis. ..
  22. Regulation of Mitochondrial Fission/Fusion by PP2A and PKA in Neurons
    Stefan Strack; Fiscal Year: 2009
    ..Our studies may ultimately lead to better therapies for stroke and neurodegenerative disorders. ..
  23. Pharmacological vaccine adjuvants: analysis of immune responses to vaccines
    Jeannine M Durdik; Fiscal Year: 2010
    ..This work will define the sorts of vaccines that these pharmacological interventions can be useful with, their potential utility in the compromised immune responses of elderly individuals, and their biochemical mechanisms of action. ..
  24. Regulation of Mammalian Oocyte Maturation
    Stephen M Downs; Fiscal Year: 2010
    ....
  25. Function and Regulation of PKA-mediated GRK Phosphorylation in Photoreceptors
    JARED DAVID CHRISPELL; Fiscal Year: 2013
    ..These studies will provide a foundation for understanding the novel role of phosphorylation by PKA on recovery and adaptation in vertebrate cones. ..
  26. Chemokine receptor-4 regulation of Beta adrenergic-mediated calcium channel
    Sima T Tarzami; Fiscal Year: 2012
    ....
  27. Hippocampal Mechanisms of Fear Extinction
    Jelena Radulovic; Fiscal Year: 2010
    ....
  28. REGULATION OF FILAMENTOUS GROWTH IN YEAST
    Haoping Liu; Fiscal Year: 2013
    ..This work will provide us with a better understanding of how C. albicans integrates various signals to control growth and development, and how it survives and grows in various host environments. ..
  29. Targeting Airway Inflammation from Concentrated Animal Feeding Operation Dust
    Debra Romberger; Fiscal Year: 2013
    ....
  30. Interactions Between p90 Ribosomal S6 Kinase and Protein Kinase A
    Tarun B Patel; Fiscal Year: 2010
    ..These novel insights may then permit the development of specific interventions that regulate certain functions of both these kinases. ..
  31. Local Mechanisms Underlying Synaptic Plasticity
    Ashok N Hegde; Fiscal Year: 2012
    ..Protein degradation is abnormal in many diseases and disorders of the brain. This research could help explain the memory loss that occurs in brain diseases and memory loss that happens in old age. ..
  32. The Role of N-myristylation and N-terminal Modifications on PKA Structure and Dyn
    ADAM CHRISTOPHER BASTIDAS; Fiscal Year: 2013
    ..The newly identified structures, dynamics, and interactions of multiple PKA holoenzymes may shape the role of PKA in many biological processes. ..
  33. Cyclic AMP Mediation of Epithelial Cell Function
    JAMES RICHARD GOLDENRING; Fiscal Year: 2012
    ..These studies will establish the roles of specific multiprotein complexes scaffolded by AKAP350 in localized regions of the cell. ..
  34. The Regulation of CBF by Adenosine
    H Winn; Fiscal Year: 2009
    ..Such knowledge is necessary to allow more rational and innovative treatments of brain ischemia, head injury and stroke. ..
  35. Ethanol on Excitation-Contraction in Cardiac Cells
    Andrew Thomas; Fiscal Year: 2009
    ..These findings may also have broader implications in elucidating the causal factors associated with the development of other aberrant adaptive processes in the heart, which eventually lead to cardiac failure ..
  36. PKA targeting: A novel mechanism for GPCR resensitization
    SULEIMAN WAKIM BAHOUTH; Fiscal Year: 2012
    ..By investigating the function of these networks, we believe that we can improve on the performance of beta-blockers, which are widely-used in treating two major health problems in America, namely hypertension and heart failure. ..
  37. Spatiotemporal regulation of beta adrenoceptor signaling in cardiacmyocytes
    Yang K Xiang; Fiscal Year: 2013
    ..We will attempt to selectively inhibit a specific PDE4D isoform by adenovirus gene transfer of PDE4D mutants into myocardium of TAC-treated animals, and examine cardiac performance in vivo. ..
  38. CRCNS: Spatial &Temporal Aspects of cAMP/PKA Signaling Underlying Information
    KIM L BLACKWELL; Fiscal Year: 2012
    ..Successful completion of the research will form the basis for investigating how alterations in this pathway contributes to psychiatric disease such as schizophrenia and alcoholism. ..
  39. A Role for Mena in the Heart
    Burns C Blaxall; Fiscal Year: 2012
    ..Heart failure is a debilitating disease with poor prognosis. This proposal aims to determine the functional role of the newly identified HF-associated gene named Mena, potentially providing novel diagnostic/therapeutic targets. ..
  40. Regulation of cAMP - Dependent Protein Kinase Genes
    GEORGE STANLEY MCKNIGHT; Fiscal Year: 2013
    ..The sensitivity of the hypothalamic response network to leptin is one of the ultimate determinants of how much energy is stored as fat and leptin resistance is one of the defining features of obesity. ..
  41. Pattern Recognition of P. gingivalis Virulence Factors
    GEORGIOS HAJISHENGALLIS; Fiscal Year: 2012
    ..We believe that CXCR4 antagonists may find therapeutic application in human periodontitis and, in this context;we will test a CXCR4 antagonist (AMD3100) for its ability to inhibit P. gingivalis-induced periodontitis in a mouse model. ..
  42. The regulation of autophagy pathways in eukaryotic cells
    Paul K Herman; Fiscal Year: 2013
    ....
  43. Understanding Mechanisms Underlying Drosophila Neurofibromatosis-1 Defects
    Andre Bernards; Fiscal Year: 2011
    ....
  44. Molecular Genetics of Carney Complex
    Cathy J Hatcher; Fiscal Year: 2010
    ....
  45. MOLECULAR ANALYSIS OF ANCHORING PROTEINS
    John D Scott; Fiscal Year: 2013
    ..RNA inference techniques and the concomitant expression of mutant AKAP forms will determine if PKC anchoring is necessary for agonist dependent and suppression of M currents and if PP2B counteracts this process. ..
  46. Role of Carboxyterminal Hypervariable Region in Rap1b Function
    Gilbert C White; Fiscal Year: 2010
    ..These findings will provide insight into how the body heals bleeding injuries, as well as the underlying cause of blood clotting conditions. ..
  47. NOVEL INSIGHTS INTO MOTOR NEURON DISEASE
    John K Fink; Fiscal Year: 2013
    ..Insights gained in this bedside-to-bench investigation will advance our knowledge of the pathogenesis and ultimately treatment for NTE-MND, ALS, and for related motor neuron disorders. ..
  48. Role of PI3 Kinase and MAP Kinase in Memory Retrieval
    Daniel R Storm; Fiscal Year: 2012
    ..This study may identify drug target sites that can be used to modulate memory retrieval and be useful clinically. For example, drugs that impair memory retrieval may be used in the treatment of phobias. ..
  49. Cross-talk between PKA, cellular tension, and Ca2+ channels during cell migration
    Alan K Howe; Fiscal Year: 2013
    ..Thus, the proposed work will provide insight into the molecular mechanisms that cells use to integrate environmental sensing with localized intracellular signaling events that control cell migration. ..
  50. High throughput assay for novel pharmacological probes targeting cAMP signaling
    Xiaodong Cheng; Fiscal Year: 2012
    ..Novel pharmacological probes targeting specific cAMP signaling components can potentially lead to the identification of mechanism-based therapeutic strategies for diseases associated with cAMP signaling. ..
  51. Mechanisms governing the compartmentalization of activated PKA
    SHANE TILLO; Fiscal Year: 2013
    ..The goal of the experiments in this application is to incorporate PKA diffusion into a model of PKA specificity in post-synaptic compartments. ..
  52. Probing the role of AKAPs in breast cancer using stapled peptide inhibitors
    Eileen J Kennedy; Fiscal Year: 2013
    ..This will be used as a foundation for studying altered kinase signaling in cancer models. ..
  53. Visualization of shear stress-induced endothelial cell signaling.
    Eugene Tkachenko; Fiscal Year: 2009
    ..These exploratory studies have the potential to enable the facile analysis of flow-mediated signaling in living endothelial cells. ..
  54. The function of ezrin in stimulus-coupled acid secretion
    Xuebiao Yao; Fiscal Year: 2012
    ....
  55. Novel Pharmacological Probes Targeting Exchange Proteins Activated by cAMP (EPAC)
    Jia Zhou; Fiscal Year: 2013
    ....
  56. An intracellular signaling switch for maintaining peripheral sensitization
    Michael R Vasko; Fiscal Year: 2013
    ..If we show that a unique pathway exists in pain conducting neurons that make them hypersensitive during inflammation, new and targeted drug therapy can be developed to shut off the pathway and treat chronic inflammatory pain. ..
  57. Mechanisms of Compartmentalized cAMP Signaling
    Jin Zhang; Fiscal Year: 2013
    ....
  58. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..A thorough physical and biochemical characterization of PDE11 will be carded out, and the likelihood of regulation of this enzyme by ligand binding to its GAF domains or by enzyme phosphorylation will be explored. ..
  59. MODULATION OF SODIUM CHANNELS BY G PROTEINS
    Todd Scheuer; Fiscal Year: 2001
    ..An understanding of how they are modulated physiologically will provide the basis for developing pharmacologic means of controlling them to achieve specific therapeutic goals. ..
  60. Beta-adrenergic Response in Cardiac Hypertrophy/Failure
    Meredith Bond; Fiscal Year: 2004
    ..Structural and functional outcomes of these changes plus identification of the altered phosphatase activity will shed light on mechanisms responsible for the functional decline in heart failure. ..
  61. HORMONAL CONTROL OF HEPATIC GLUCONEOGENESIS/GLYCOLYSIS
    Alex Lange; Fiscal Year: 2005
    ..abstract_text> ..
  62. CYLIC AMP REGULATION OF PROTEIN SERETION
    MICHAEL UHLER; Fiscal Year: 1991
    ....
  63. Regulation of Integrin Alpha4 Betal
    MARK HOWARD GINSBERG; Fiscal Year: 2010
    ..These fundamental studies will provide new insight into the regulation of inflammation and will test and advance paradigms that could lead to novel therapies for Rheumatic Diseases. ..