adenylate cyclase

Summary

Summary: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.

Top Publications

  1. pmc Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase
    Sungwon An
    Department of Biology, Washington University, St Louis, MO 63130 4899, USA
    J Neurophysiol 105:2289-96. 2011
  2. pmc Inhibitors of membranous adenylyl cyclases
    Roland Seifert
    Institute of Pharmacology, Medical School of Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Trends Pharmacol Sci 33:64-78. 2012
  3. pmc Roles of protein kinase A and adenylate cyclase in light-modulated cellulase regulation in Trichoderma reesei
    Andre Schuster
    Research Area of Gene Technology and Applied Biochemistry, Institute for Chemical Engineering, Vienna University of Technology, Vienna, Austria
    Appl Environ Microbiol 78:2168-78. 2012
  4. ncbi Capturing adenylyl cyclases as potential drug targets
    Sandra Pierre
    Pharmazentrum Frankfurt, ZAFES, Institut fur Klinische Pharmakologie, Klinikum der Goethe Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Drug Discov 8:321-35. 2009
  5. ncbi Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway
    Matthew C Wolfgang
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 4:253-63. 2003
  6. pmc The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila
    Laura B Duvall
    Department of Anatomy and Neurobiology, Washington University Medical School, St Louis, Missouri, United States of America
    PLoS Biol 10:e1001337. 2012
  7. ncbi The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:8949-54. 2003
  8. ncbi Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor
    Y Chen
    Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 289:625-8. 2000
  9. 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
  10. ncbi Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase
    Nisheeth Agarwal
    Department of Medicine, Johns Hopkins School of Medicine, CRB2, Room 1 08, 1550 Orleans Street, Baltimore, Maryland 21231 1044, USA
    Nature 460:98-102. 2009

Detail Information

Publications361 found, 100 shown here

  1. pmc Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase
    Sungwon An
    Department of Biology, Washington University, St Louis, MO 63130 4899, USA
    J Neurophysiol 105:2289-96. 2011
    ..Unlike VIP-mediated signaling in other cell types, simultaneous antagonism of adenylate cyclase and phospholipase C activities was required to block the VIP-induced phase shifts of SCN rhythms...
  2. pmc Inhibitors of membranous adenylyl cyclases
    Roland Seifert
    Institute of Pharmacology, Medical School of Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Trends Pharmacol Sci 33:64-78. 2012
    ..Future strategies for the development of the mAC inhibitor field are discussed critically...
  3. pmc Roles of protein kinase A and adenylate cyclase in light-modulated cellulase regulation in Trichoderma reesei
    Andre Schuster
    Research Area of Gene Technology and Applied Biochemistry, Institute for Chemical Engineering, Vienna University of Technology, Vienna, Austria
    Appl Environ Microbiol 78:2168-78. 2012
    ..We were therefore interested in how the crucial components of this pathway, adenylate cyclase (ACY1) and cAMP-dependent protein kinase A (PKA), would affect cellulase gene expression...
  4. ncbi Capturing adenylyl cyclases as potential drug targets
    Sandra Pierre
    Pharmazentrum Frankfurt, ZAFES, Institut fur Klinische Pharmakologie, Klinikum der Goethe Universität Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Rev Drug Discov 8:321-35. 2009
    ..Here we discuss the therapeutic potential of isoform-selective compounds in various clinical settings, including neuropathic pain, neurodegenerative disorders, congestive heart failure, asthma and male contraception...
  5. ncbi Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway
    Matthew C Wolfgang
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 4:253-63. 2003
    ..the TTSS led to the identification of a signaling pathway that originates from a membrane-associated adenylate cyclase and controls TTSS gene expression...
  6. pmc The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila
    Laura B Duvall
    Department of Anatomy and Neurobiology, Washington University Medical School, St Louis, Missouri, United States of America
    PLoS Biol 10:e1001337. 2012
    ..circadian pacemaker neurons? Using live imaging of intact fly brains and transgenic RNAi, we show that adenylate cyclase AC3 underlies PDF signaling in M cells...
  7. ncbi The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes
    Biplab Dasgupta
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 23:8949-54. 2003
    ..These results demonstrate that neurofibromin positively influences cAMP generation and activation of cAMP growth regulatory targets in astrocytes and expands the role of the NF1 gene in astrocyte growth regulation...
  8. ncbi Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor
    Y Chen
    Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 289:625-8. 2000
    ..sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems...
  9. 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
    ..Extensive information has been obtained on the core section of the pathway, i.e. Cdc25, Ras, adenylate cyclase, PKA, and on components interacting directly with this core section, such as the Ira proteins, Cap/Srv2 and ..
  10. ncbi Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase
    Nisheeth Agarwal
    Department of Medicine, Johns Hopkins School of Medicine, CRB2, Room 1 08, 1550 Orleans Street, Baltimore, Maryland 21231 1044, USA
    Nature 460:98-102. 2009
    ..Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence...
  11. pmc The "soluble" adenylyl cyclase in sperm mediates multiple signaling events required for fertilization
    Kenneth C Hess
    Department of Pharmacology, Joan and Sanford Weill Medical College, Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA
    Dev Cell 9:249-59. 2005
    ..This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC...
  12. ncbi Adenylyl cyclase localization regulates streaming during chemotaxis
    Paul W Kriebel
    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Building 37 Room 1E24, Bethesda, MD 20892, USA
    Cell 112:549-60. 2003
    ..This could represent a general mechanism that cells use to amplify chemotactic responses...
  13. ncbi Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain
    Georgia A Bishop
    Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
    J Comp Neurol 505:562-71. 2007
    ..Overall, our data indicate that ACIII is a prominent marker of primary cilia in the brain and will provide an important tool to facilitate further investigations into the functions of these organelles...
  14. pmc Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight
    Rachel M Freathy
    Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Nat Genet 42:430-5. 2010
    ..The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy...
  15. ncbi In yeast, RAS proteins are controlling elements of adenylate cyclase
    T Toda
    Cell 40:27-36. 1985
    ..Yeast strains carrying the IAC mutation have elevated levels of adenylate cyclase activity. bcy1 is a mutation that suppresses the lethality in adenylate cyclase deficient yeast...
  16. pmc cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells
    Teodor G Paunescu
    MGH Center for Systems Biology, Program in Membrane Biology, and Division of Nephrology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114, USA
    Am J Physiol Renal Physiol 298:F643-54. 2010
    ....
  17. ncbi Adenylyl cyclase regulates heavy metal sensitivity, bikaverin production and plant tissue colonization in Fusarium proliferatum
    Gabor Kohut
    Agricultural Biotechnology Center, Mycology Group of the Hungarian Academy of Sciences, Institute of Plant Protection, Szent Istvan University, Godollo, Hungary
    J Basic Microbiol 50:59-71. 2010
    ..This finding provides further evidence of the role of the cAMP-PKA pathway in regulating bikaverin production...
  18. ncbi Identification of a specialized adenylyl cyclase that may mediate odorant detection
    H A Bakalyar
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205
    Science 250:1403-6. 1990
    ..This property may represent one mechanism of achieving sensitivity in odorant perception...
  19. pmc Cloning and characterization of a Drosophila serotonin receptor that activates adenylate cyclase
    P Witz
    Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184 de Génie Génétique et de Biologie Moléculaire, Faculte de Medecine, Strasbourg, France
    Proc Natl Acad Sci U S A 87:8940-4. 1990
    ..When stably introduced into mouse NIH 3T3 cells, the 5HT-dro receptor activates adenylate cyclase in response to serotonin and is inhibited by serotonin receptor antagonists such as dihydroergocryptine...
  20. pmc Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals
    J Buck
    Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 96:79-84. 1999
    ..The two presumptive catalytic domains of sAC are closely related to cyanobacterial adenylyl cyclases, providing an evolutionary link between bacterial and mammalian signaling molecules...
  21. pmc An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia
    Roger S Smith
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Infect Immun 72:1677-84. 2004
    ..Finally, we demonstrate that virulence can be restored in an adenylate cyclase mutant by the overexpression of exsA, which specifically restores expression of the type III secretion ..
  22. pmc Dynamic regulation of cAMP synthesis through anchored PKA-adenylyl cyclase V/VI complexes
    Andrea L Bauman
    Howard Hughes Medical Institute, Vollum Institute, L 474, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA
    Mol Cell 23:925-31. 2006
    ..This protein configuration permits the formation of a negative feedback loop that temporally regulates cAMP production...
  23. pmc Characterization of phylogenetically distant members of the adenylate cyclase family from mycobacteria: Rv1647 from Mycobacterium tuberculosis and its orthologue ML1399 from M. leprae
    Avinash R Shenoy
    Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India
    Biochem J 387:541-51. 2005
    ..Rv1647 was predicted to be an active adenylate cyclase but its position in a phylogenetically distant branch from the other enzymes characterized so far from M...
  24. ncbi Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins
    D Broek
    Cell 41:763-9. 1985
    ..purified RAS proteins, whether derived from the yeast RAS1 or RAS2 or the human H-ras genes, activate yeast adenylate cyclase in the presence of guanine nucleotides...
  25. pmc Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions
    Meinhard Schiller
    Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, 48149 Munster, Germany
    J Biol Chem 285:409-21. 2010
    ..Our findings identify the cAMP pathway as a potent but differential and promoter-specific regulator of TGF-beta-mediated effects involved in extracellular matrix homeostasis...
  26. pmc Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
    Richa Saxena
    Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 42:142-8. 2010
    ..Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18))...
  27. pmc N-acetylglucosamine induces white to opaque switching, a mating prerequisite in Candida albicans
    Guanghua Huang
    Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America
    PLoS Pathog 6:e1000806. 2010
    ..Our results therefore suggest that signals produced by bacterial co-members of the gastrointestinal tract microbiota regulate switching and therefore mating of C. albicans...
  28. pmc Adenylate cyclase and the cyclic AMP receptor protein modulate stress resistance and virulence capacity of uropathogenic Escherichia coli
    Grant T Donovan
    Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, Utah, USA
    Infect Immun 81:249-58. 2013
    ..We conclude that balanced input from many cAMP-CRP-responsive elements, including RpoS, is critical to the ability of UPEC to handle the nutrient limitations and severe environmental stresses present within the mammalian urinary tract...
  29. ncbi cAMP and ras signalling independently control spore germination in the filamentous fungus Aspergillus nidulans
    Sabine Fillinger
    Unité Microbiologie et Environnement, CNRS URA 2172, Institut Pasteur, Paris, France
    Mol Microbiol 44:1001-16. 2002
    ..A. nidulans strains defective for adenylate cyclase (CyaA) or for the functionally overlapping cAMP-dependent protein kinase (PkaA) and newly characterized SchA ..
  30. ncbi Regulation of ovarian steroidogenesis in vitro by gonadotropin in common carp Cyprinus carpio: interaction between calcium- and adenylate cyclase-dependent pathways and involvement of ERK signaling cascade
    Sudipta Paul
    Endocrinology Laboratory, Department of Zoology, University of Kalyani, Kalyani, West Bengal, India
    J Mol Endocrinol 45:207-18. 2010
    ..calmodulin attenuated human chorionic gonadotropin (HCG)-induced steroid production, whereas modulators of adenylate cyclase and protein kinase A (PKA) increased their production, indicating that both calcium- and PKA-dependent ..
  31. ncbi Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress
    Satoshi Okumura
    Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan
    Circulation 116:1776-83. 2007
    ..Molecular mechanisms of desensitization have been well studied at the level of adrenergic receptors but less so at the level of the effector enzyme, adenylyl cyclase (AC)...
  32. ncbi Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells
    B Roger
    Universite de Bordeaux 1, Institut Europeen de Chimie et Biologie, UMR CNRS 5248, 2 Av Robert Escarpit, 33607 Pessac, France
    Diabetologia 54:390-402. 2011
    ..We therefore investigated long-term effects of glucose on this pathway with special regard to the incretin glucagon-like peptide 1 (GLP-1)...
  33. ncbi Extracellular calcium influx activates adenylate cyclase 1 and potentiates insulin secretion in MIN6 cells
    Tetsuya Kitaguchi
    Life Function and Dynamics, ERATO, JST Japan Science and Technology Agency, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Biochem J 450:365-73. 2013
    ..We performed RT (reverse transcription)-PCR analysis and found that Ca(2+)-sensitive Adcy1 (adenylate cyclase 1) was expressed in MIN6 cells...
  34. pmc Intracellular cAMP signaling by soluble adenylyl cyclase
    Martin Tresguerres
    Marine Biology Research Division, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA
    Kidney Int 79:1277-88. 2011
    ..In this review, we detail the known functions of sAC, and we reassess commonly held views of cAMP signaling inside cells...
  35. pmc Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies
    Rachna Sadana
    Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
    Neurosignals 17:5-22. 2009
    ..In this review we explore the latest on AC knockout and overexpression studies to better understand the roles of G protein regulation of ACs in the brain, olfactory bulb, and heart...
  36. pmc A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen
    Clemens Steegborn
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 280:31754-9. 2005
    ..This novel inhibition mechanism likely applies to other adenylyl cyclase inhibitors, and the identified ligand-binding site has important implications for the development of specific adenylyl cyclase inhibitors...
  37. pmc Adenylate cyclase activity of Pseudomonas aeruginosa ExoY can mediate bleb-niche formation in epithelial cells and contributes to virulence
    Victoria Hritonenko
    School of Optometry, University of California, Berkeley, CA 94720, USA
    Microb Pathog 51:305-12. 2011
    ..In contrast, plasmid expression of any of four adenylate cyclase mutant forms of exoY did not enable bleb-niche formation, and bacteria localized to perinuclear vacuoles as ..
  38. ncbi Mutations in the carboxy-terminus of the third intracellular loop of the human recombinant VPAC1 receptor impair VIP-stimulated [Ca2+]i increase but not adenylate cyclase stimulation
    Ingrid Langer
    Department of Biological Chemistry and Nutrition, Faculty of Medicine, Universite Libre de Bruxelles, Campus Erasme, Bat G E, 808 route de Lennik CP611, B 1070 Brussels, Belgium
    Cell Signal 17:17-24. 2005
    ..intestinal polypeptide (VIP) VPAC1 receptor is preferentially coupled to Galphas protein that stimulates adenylate cyclase activity and also to Galphaq and Galphai proteins that stimulate the inositol phosphate/calcium pathway...
  39. pmc The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans
    Rebecca A Hall
    School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom
    Eukaryot Cell 10:1034-42. 2011
    ....
  40. ncbi Sensitization of adenylate cyclase by Galpha i/o-coupled receptors
    Val J Watts
    Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA
    Pharmacol Ther 106:405-21. 2005
    ..Acute activation inhibits the activity of adenylate cyclase, thereby attenuating cyclic AMP accumulation; in contrast, persistent activation of Galpha i/o-coupled ..
  41. ncbi Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors
    C C Felder
    Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA
    Mol Pharmacol 48:443-50. 1995
    ..Except for its inability to couple to the modulation of Q-type calcium channels or inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar pharmacological and biochemical properties...
  42. pmc Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types
    Allison L Blum
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Curr Biol 19:1341-50. 2009
    ..At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view...
  43. ncbi The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein
    Elzbieta Kojro
    Institute of Biochemistry, Johannes Gutenberg University, Becherweg, Mainz, Germany
    FASEB J 20:512-4. 2006
    The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has neurotrophic as well as anti-apoptotic properties and is involved in learning and memory processes...
  44. ncbi Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase
    R S Ostrom
    Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 276:42063-9. 2001
    ..Therefore, spatial co-localization is a key determinant of efficiency of coupling by particular extracellular signals to activation of GPCR-linked effectors...
  45. pmc Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans
    C R Rocha
    Eukaryotic Genetics Group, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada
    Mol Biol Cell 12:3631-43. 2001
    ..These findings suggest that fungal adenylyl cyclases and other regulators of the cAMP signaling pathway may be useful targets for antifungal drugs...
  46. ncbi Fast manipulation of cellular cAMP level by light in vivo
    Saskia Schröder-Lang
    Max Planck Institut fur Biophysik, 60439 Frankfurt, Germany
    Nat Methods 4:39-42. 2007
    ..The activity of PACs is strongly and reversibly enhanced by blue light, providing a powerful tool for light-induced manipulation of cAMP in animal cells...
  47. ncbi Differential roles of the fan-shaped body and the ellipsoid body in Drosophila visual pattern memory
    Yufeng Pan
    State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, People s Republic of China
    Learn Mem 16:289-95. 2009
    ..Our study defines a complex neural circuit in the central complex for Drosophila visual pattern memory...
  48. ncbi Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells
    A Miyata
    U S Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, LA 70037
    Biochem Biophys Res Commun 164:567-74. 1989
    A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues...
  49. pmc Adenylate cyclase regulates elongation of mammalian primary cilia
    Young Ou
    Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1
    Exp Cell Res 315:2802-17. 2009
    ..We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation...
  50. 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
    The activity of adenylate cyclase in the yeast Saccharomyces cerevisiae is controlled by two G-protein systems, the Ras proteins and the Galpha protein Gpa2...
  51. pmc cAMP-dependent signaling as a core component of the mammalian circadian pacemaker
    John S O'Neill
    Medical Research Council MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Science 320:949-53. 2008
    ..We propose that daily activation of cAMP signaling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles...
  52. pmc Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis
    Amber Davis-Hanna
    Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Microbiol 67:47-62. 2008
    ..Because several cAMP-controlled outputs are affected by farnesol and dodecanol, our findings suggest that these compounds impact activity of the Ras1-Cdc35 pathway, thus leading to an alteration of C. albicans morphology...
  53. ncbi Forskolin as a tool for examining adenylyl cyclase expression, regulation, and G protein signaling
    Paul A Insel
    Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093 0636, USA
    Cell Mol Neurobiol 23:305-14. 2003
    ....
  54. pmc CO(2) regulates white-to-opaque switching in Candida albicans
    Guanghua Huang
    Department of Biology, The University of Iowa, Iowa City, 52242, USA
    Curr Biol 19:330-4. 2009
    ..It exerts this control equally under anaerobic and aerobic conditions. These results suggest that the high levels of CO(2) in the host induce and stabilize the opaque phenotype, thus facilitating mating...
  55. pmc Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus
    Chun Kim
    Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 105:6150-5. 2008
    ..anthracis...
  56. pmc Localization of cardiac L-type Ca(2+) channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation
    Ravi C Balijepalli
    Department of Medicine, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 103:7500-5. 2006
    ..These findings demonstrate that subcellular localization of L-type Ca(2+) channels to caveolar macromolecular signaling complexes is essential for regulation of the channels by specific signaling pathways...
  57. pmc Adenylyl cyclase--A-kinase anchoring protein complexes: the next dimension in cAMP signaling
    Carmen W Dessauer
    Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
    Mol Pharmacol 76:935-41. 2009
    ..The ability of AKAPs to assemble intricate feedback loops to control spatiotemporal aspects of cAMP signaling adds yet another dimension to the classic cAMP pathway...
  58. pmc Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor
    Yuequan Shen
    Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA
    EMBO J 24:929-41. 2005
    ..Mammalian adenylyl cyclases share no structural similarity with EF and they also use two-metal-ion catalysis, suggesting the catalytic mechanism-driven convergent evolution of two structurally diverse adenylyl cyclases...
  59. ncbi Structures, mechanism, regulation and evolution of class III nucleotidyl cyclases
    S C Sinha
    University of Texas Southwestern Medical Center, Division of Infectious Diseases, Department of Internal Medicine, 5323 Harry Hines Blvd, Dallas 75390 9113, USA
    Rev Physiol Biochem Pharmacol 157:105-40. 2006
    ..Many of these regulators act by altering the interface of the catalytic domains and therefore the integrity of the catalytic site(s). This review focuses on both conserved and divergent mechanisms of class III NC function and regulation...
  60. ncbi Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases
    Feng Wei
    Department of Anesthesiology, Washington University Pain Center, Washington University, St Louis, MO 63108, USA
    Neuron 36:713-26. 2002
    ..Intra-ACC administration of forskolin rescued behavioral allodynia defective in the AC1&8 DKO mice. Our studies suggest that AC1 and AC8 in the ACC selectively contribute to behavioral allodynia...
  61. ncbi Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1
    Susumu Katsuma
    Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611 0011, Japan
    Biochem Biophys Res Commun 329:386-90. 2005
    ..Bile acids induced rapid and dose-dependent elevation of intracellular cAMP levels in STC-1 cells. An adenylate cyclase inhibitor, MDL12330A, significantly suppressed bile acid-promoted GLP-1 secretion, suggesting that bile ..
  62. ncbi Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38)
    A Miyata
    U S Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, LA 70037
    Biochem Biophys Res Commun 170:643-8. 1990
    ..neuropeptide with 38 residues (PACAP38) was isolated from ovine hypothalamic tissues using the pituitary adenylate cyclase activation in rat pituitary cell cultures as a parameter of the biological activity (Miyata et al, Biochem...
  63. pmc Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence
    Torsten Klengel
    Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom
    Curr Biol 15:2021-6. 2005
    ..Novel therapeutic agents could target this pathway at several levels to control fungal infections...
  64. ncbi Two-metal-Ion catalysis in adenylyl cyclase
    J J Tesmer
    Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 285:756-60. 1999
    ..The similarity of the active site of AC to those of DNA polymerases suggests that the enzymes catalyze phosphoryl transfer by the same two-metal-ion mechanism and likely have evolved from a common ancestor...
  65. ncbi Characterization of mouse heart adenylyl cyclase
    Martin Göttle
    Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany
    J Pharmacol Exp Ther 329:1156-65. 2009
    ..Moreover, lack of antibody specificity and Mn(2+) masking AC5 effects were problems...
  66. pmc Phosphoinositide 3-kinase activity controls the chemoattractant-mediated activation and adaptation of adenylyl cyclase
    Frank I Comer
    Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4256, USA
    Mol Biol Cell 17:357-66. 2006
    ..Thus, PI3K activity is poised to regulate both ACA activation and adaptation, thereby providing a link to ensure the proper balance of counteracting signals required to maintain optimal chemoresponsiveness...
  67. pmc Role of adenylate cyclase 1 in retinofugal map development
    Onkar S Dhande
    Department of Neurobiology, Yale University, New Haven, Connecticut 06510, USA
    J Comp Neurol 520:1562-83. 2012
    The development of topographic maps of the sensory periphery is sensitive to the disruption of adenylate cyclase 1 (AC1) signaling...
  68. ncbi A soluble adenylyl cyclase from sea urchin spermatozoa
    Mamoru Nomura
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093 0202, USA
    Gene 353:231-8. 2005
    ..This implies (as shown in mouse) that susAC has a role in sperm motility, most probably through axonemal protein phosphorylation or ion channel regulation...
  69. ncbi Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9)
    B M Hacker
    Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA
    Genomics 50:97-104. 1998
    ..In contrast to mouse AC9, the activity of human AC9 is unaffected by inhibitors of calcineurin. These data emphasize the importance of determining the regulatory properties of human adenylyl cyclases...
  70. ncbi Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells
    K Moens
    Diabetes Research Center, Vrije Universiteit Brussel, Belgium
    Diabetes 45:257-61. 1996
    ..In conclusion, these data show that stimulation of glucagon, GLP-I, and GIP receptors in rat beta-cells causes cAMP production required for insulin release, while adenylate cyclase in alpha-cells is positively regulated by GIP.
  71. pmc Molecular details of cAMP generation in mammalian cells: a tale of two systems
    Margarita Kamenetsky
    Department of Pharmacology, Joan and Sanford I Weill Medical College of Cornell University, New York, NY 10021, USA
    J Mol Biol 362:623-39. 2006
    ..This comparison reveals the mechanisms underlying their different properties but also illustrates many unifying themes for these evolutionary related signaling enzymes...
  72. ncbi Broad specificity of mammalian adenylyl cyclase for interaction with 2',3'-substituted purine- and pyrimidine nucleotide inhibitors
    Tung Chung Mou
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9050, USA
    Mol Pharmacol 70:878-86. 2006
    ..The mAC binding site exhibits broad specificity, accommodating various bases and fluorescent groups at the 2',3'-O-ribosyl position. These data should greatly facilitate the rational design of potent, isoform-selective mAC inhibitors...
  73. 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
    ..2 intramuscular injections. Spinal blockade of adenylate cyclase prevents the expected increase in p-CREB that occurs after intramuscular acid injection...
  74. pmc Drosophila FoxO regulates organism size and stress resistance through an adenylate cyclase
    Jaakko Mattila
    Department of Molecular Profiling, Merck Research Laboratories, 126 East Lincoln Ave, RY80M 179, Rahway, NJ 07065, USA
    Mol Cell Biol 29:5357-65. 2009
    ..that Drosophila melanogaster FoxO (dFoxO) regulates cAMP signaling by directly inducing the expression of an adenylate cyclase gene, ac76e...
  75. ncbi B96Bom encodes a Bombyx mori tyramine receptor negatively coupled to adenylate cyclase
    H Ohta
    Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane, Japan
    Insect Mol Biol 12:217-23. 2003
    ..mori TA receptor, which is negatively coupled to adenylate cyclase. The use of this expression system should facilitate physiological studies of TA receptors as well as ..
  76. ncbi Targeted knockdown of G protein subunits selectively prevents receptor-mediated modulation of effectors and reveals complex changes in non-targeted signaling proteins
    Andrejs M Krumins
    Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Biol Chem 281:10250-62. 2006
    ..These findings provide a foundation for understanding the mechanisms that regulate the adaptability and remarkable resilience of G protein signaling networks...
  77. pmc Adult type 3 adenylyl cyclase-deficient mice are obese
    Zhenshan Wang
    Department of Pharmacology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 4:e6979. 2009
    ..Therefore, we examined the weight of AC3 mice over an extended period of time...
  78. ncbi Adenylyl cyclases as innovative therapeutic goals
    Barbara Pavan
    Department of Biology and Evolution, General Physiology Section, University of Ferrara, Ferrara, Italy
    Drug Discov Today 14:982-91. 2009
    ..In this review, the potential of AC as the object of drug therapy is discussed...
  79. ncbi Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate
    Tung Chung Mou
    Department of Biochemistry, Howard Hughes Medical Institute, The University of Texas Southwestern Medical, Dallas, Texas 75390 9050, USA
    J Biol Chem 280:7253-61. 2005
    ..Mutational analysis of two non-conserved amino acids in the MANT-binding pocket suggests that residues outside of the binding site influence isoform selectivity toward MANT-GTP...
  80. pmc Regulation and organization of adenylyl cyclases and cAMP
    Dermot M F Cooper
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK
    Biochem J 375:517-29. 2003
    ..Microdomains are a consequence of these solutions, in which cAMP dynamics may differ from the broad cytosol. Currently evolving methodologies are beginning to reveal cAMP fluctuations in these various compartments...
  81. pmc The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation
    Kathleen Freson
    Center for Molecular and Vascular Biology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
    J Clin Invest 113:905-12. 2004
    The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide of the vasoactive intestinal peptide/secretin/glucagon superfamily...
  82. ncbi A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2
    M A Davare
    Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA
    Science 293:98-101. 2001
    ..The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor...
  83. pmc The adenylyl cyclase activity of anthrax edema factor
    Wei Jen Tang
    Ben May Department for Cancer Research, The University of Chicago, 929 East 57th Street, GCIS W434, Chicago, IL 60637, USA
    Mol Aspects Med 30:423-30. 2009
    ..Comparison of the biochemical and structural characteristics of these two AC toxins with host ACs reveal that they have diverse strategies of catalytic activation, yet use the same two-metal-ion catalytic mechanism...
  84. pmc GSK3beta mediates renal response to vasopressin by modulating adenylate cyclase activity
    Reena Rao
    Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Am Soc Nephrol 21:428-37. 2010
    ..Both GSK3beta gene deletion and pharmacologic inhibition of GSK3beta reduced adenylate cyclase activity...
  85. ncbi Mapping the anthrax protective antigen binding site on the lethal and edema factors
    D Borden Lacy
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:3006-10. 2002
    ..The seven mutation-sensitive amino acids are clustered on the surface of LF and form a small convoluted patch with both hydrophobic and hydrophilic character. We propose that this patch constitutes the recognition site for PA...
  86. ncbi Interspecies trait genetics reveals association of Adcy8 with mouse avoidance behavior and a human mood disorder
    Annetrude J G de Mooij-van Malsen
    Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, 3584 CG Utrecht, The Netherlands
    Biol Psychiatry 66:1123-30. 2009
    ..This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior...
  87. ncbi 2'(3')-O-(N-methylanthraniloyl)-substituted GTP analogs: a novel class of potent competitive adenylyl cyclase inhibitors
    Andreas Gille
    Department of Pharmacology and Toxicology, The University of Kansas, Lawrence, Kansas 66045 7582, USA
    J Biol Chem 278:12672-9. 2003
    ..Instead, MANT-GTP gamma S/MANT-GppNHp constitute a novel class of potent competitive AC inhibitors...
  88. ncbi Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling
    Debbie Willoughby
    Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK
    Sci Signal 5:ra29. 2012
    ....
  89. ncbi Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase
    A Angers
    Departement de Biochimie, Universite de Montreal, Montreal, Quebec, Canada H3C 3J7
    J Neurosci 18:5586-93. 1998
    ..5-HTap1 is thus negatively coupled to adenylate cyclase. The production of antiserum against the 5-HTap1 receptor allowed us to examine its expression in animal ..
  90. pmc Novel inhibitors of anthrax edema factor
    Deliang Chen
    Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555 0857, USA
    Bioorg Med Chem 16:7225-33. 2008
    ..Thus, the fragment-based pharmacophore identified a small number of diverse compounds for assay, and greatly enhanced the selection process of advanced lead compounds for combinatorial design...
  91. pmc Bis-halogen-anthraniloyl-substituted nucleoside 5'-triphosphates as potent and selective inhibitors of Bordetella pertussis adenylyl cyclase toxin
    Jens Geduhn
    Institute of Organic Chemistry, University of Regensburg, Regensburg, Germany
    J Pharmacol Exp Ther 336:104-15. 2011
    ..Collectively, we have identified the first potent CyaA inhibitor with high selectivity relative to mammalian ACs. The fluorescence properties of bis-ANT nucleotides facilitate development of a high-throughput screening assay...
  92. pmc AKAP79/150 interacts with AC8 and regulates Ca2+-dependent cAMP synthesis in pancreatic and neuronal systems
    Debbie Willoughby
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    J Biol Chem 285:20328-42. 2010
    ....
  93. pmc Adenylate cyclase in Saccharomyces cerevisiae is a peripheral membrane protein
    M R Mitts
    School of Pharmacy, University of Wisconsin, Madison 53706
    Mol Cell Biol 10:3873-83. 1990
    The adenylate cyclase system of the yeast Saccharomyces cerevisiae contains the CYR1 polypeptide, responsible for catalyzing formation of cyclic AMP (cAMP) from ATP, and two RAS polypeptides, which mediate stimulation of cAMP synthesis ..
  94. ncbi Anthrax edema factor potency depends on mode of cell entry
    Jia Hong
    Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA
    Biochem Biophys Res Commun 335:850-7. 2005
    ..These results indicate that the effects of EF in cells can differ dependent upon the mode of cellular entry of the adenylyl cyclase...
  95. pmc Structural basis for inhibition of mammalian adenylyl cyclase by calcium
    Tung Chung Mou
    Center for Biomolecular Structure and Dynamics and Division of Biological Sciences, The University of Montana, Missoula, Montana 59812, USA
    Biochemistry 48:3387-97. 2009
    ..In the latter complexes, Ca(2+) and Mg(2+) bind only to the high-affinity "B" metal site associated with substrate/product stabilization. Ca(2+) thus stabilizes the inactive conformation in both ATP- and PP(i)-bound states...
  96. pmc Role of phosphodiesterase and adenylate cyclase isozymes in murine colonic glucagon-like peptide 1 secreting cells
    Ronn S Friedlander
    Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
    Br J Pharmacol 163:261-71. 2011
    ..adenosine monophosphate (cAMP) has been shown to be a strong stimulus for GLP-1 secretion and here we investigate the activities of adenylate cyclase (AC) and phosphodiesterase (PDE) isozymes likely to shape cAMP responses in L-cells.
  97. pmc Role of carbonic anhydrase IV in the bicarbonate-mediated activation of murine and human sperm
    Petra M Wandernoth
    Department of Anatomy and Cell Biology, Saarland University, Homburg, Saar, Germany
    PLoS ONE 5:e15061. 2010
    ..06±0.20 Hz to 5.29±0.47 Hz. We show, for the first time, a physiological role of CA IV that supplies sperm with HCO(3) (-), which is necessary for stimulation of sAC and hence early activation of spermatozoa...
  98. pmc Structure-based redesign of an edema toxin inhibitor
    Deliang Chen
    Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, UTMB, Galveston, TX 77555 0857, USA
    Bioorg Med Chem 20:368-76. 2012
    ..Several derivatives demonstrated superior pharmacological properties compared to our initial lead compound, and are promising candidates to treat anthrax infections and diarrheal diseases induced by toxin-producing bacteria...
  99. pmc Interaction of the two cytosolic domains of mammalian adenylyl cyclase
    R E Whisnant
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235, USA
    Proc Natl Acad Sci U S A 93:6621-5. 1996
    ..These data suggest a model wherein either Gsalpha or forskolin enhances association of the other activator with adenylyl cyclase, as well as facilitating the interaction between the C1 and C2 domains of the enzyme...
  100. ncbi The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway
    D Broek
    Cell 48:789-99. 1987
    ..Cells lacking CDC25 have low levels of cyclic AMP and decreased levels of Mg2+-dependent adenylate cyclase activity...
  101. pmc Separate elements within a single IQ-like motif in adenylyl cyclase type 8 impart ca2+/calmodulin binding and autoinhibition
    David A MacDougall
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom
    J Biol Chem 284:15573-88. 2009
    ..These data support a sophisticated activation mechanism of AC8 by CaM, in which the duality of the IQlm function is critical...

Research Grants67

  1. Modulation of cancer prevention by social stress
    Hildegard M Schuller; Fiscal Year: 2010
    ....
  2. Role of G-gamma-7 in striatal cannabinoid and D2 dopamine
    Dana E Selley; Fiscal Year: 2010
    ..These studies will provide information that contributes to our understanding of the neural mechanisms of drug addiction and possibly neuropsychiatric and movement disorders, such as schizophrenia and Parkinsonism. ..
  3. Dopamine D1 Receptor in mouse models of primary dystonia
    Laurie J Ozelius; Fiscal Year: 2013
    ..Identification of a final common pathway in different forms of EOTD will aid in directing discovery of therapeutic targets for this currently incurable disorder. ..
  4. Lipid Metabolism and Steatosis in Liver
    Amrita Kamat; Fiscal Year: 2013
    ..The study is expected to have an important impact by defining new molecular targets for the prevention and/or treatment of NAFLD and its complications. ..
  5. Development of an effective therapy against post-exposure Anthrax
    Maurizio Pellecchia; Fiscal Year: 2010
    ..antigen (PA), lethal factor (LF, a Zn2+ dependant metalloproteinase) and calmodulin-activated edema factor adenylate cyclase (EF)...
  6. Cyclic AMP Signaling in Pseudomonas aeruginosa Virulence
    Matthew C Wolfgang; Fiscal Year: 2011
    ..We hypothesize that CyaB, a membrane-anchored adenylate cyclase, initiates a P. aeruginosa virulence program by producing cAMP in response to host cues...
  7. Primate Fetal Adrenal Development: Impact on Physiological Processes After Birth
    Eugene D Albrecht; Fiscal Year: 2013
    ..and MRAP and consequently expression of: (a) IGF-II/IGFR and the cyclins required for growth of and (b) adenylate cyclase and the low density lipoprotein (LDL)R and enzymes required for DHA/DHAS synthesis by the fetal zone of the ..
  8. Analyzing Anthrax Toxins in Drosophilia
    Ethan Bier; Fiscal Year: 2013
    ..EF (a highly active adenylate cyclase) reduces the levels and activity of a small GTPase (Rab11) required in the final step of endocytic recycling ..
  9. Regulatory targets and pathogenic mechanisms of anthrax edema factor
    Jin Mo Park; Fiscal Year: 2011
    ..We found that EF, with its adenylate cyclase activity, promotes motility and survival of macrophages in vitro...
  10. Bordetella Cyclase Toxin:Effect on Leukocytes and Respiratory Epithelial Cells
    Erik L Hewlett; Fiscal Year: 2013
    ..b>Adenylate cyclase toxin (ACT) is a B...
  11. Modulation of insulin and glucagon secretion by GPCR ligands
    TARA ASHLEY SCHWETZ; Fiscal Year: 2011
    ....
  12. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard A Rockman; Fiscal Year: 2013
    ..Furthermore, the proposed studies will lead to new targets to treat cardiac hypertrophy and heart failure in humans. ..
  13. Coleus forskohlii extract: melanization and UV protection by a natural product
    JOHN DORAZIO; Fiscal Year: 2009
    ..caused by defective signaling in melanocytes by the melanocortin-1 receptor (MC1R), a protein that mediates adenylate cyclase activation and cAMP generation when bound by its natural ligand, melanocyte stimulating hormone (MSH)...
  14. Phosphorylation Events During Sperm Capacitation
    PABLO EDUARDO VISCONTI; Fiscal Year: 2013
    ..Accomplishment of these goals will lead to novel insights in clinical diagnosis of male infertility and provide tools for evaluating pharmacological contraceptive targets. ..
  15. Blood Pressure Regulation: Novel Roles for the Kidney
    Pablo A Ortiz; Fiscal Year: 2013
    ..Thus it will accelerate acquisition of knowledge of the novel mechanisms by which the kidney regulates blood pressure, and may provide new targets for anti-hypertensive drugs. ..
  16. Novel STIM1-dependent cyclic AMP signaling pathway in colonic epithelial function
    Aldebaran M Hofer; Fiscal Year: 2013
    ....
  17. MRP4 extrudes cAMP for localized regulation of calcium channel activity
    OLIVIA RUTH BUONARATI; Fiscal Year: 2013
    ..2-associated disorders in the central nervous system, including stroke, depression, anxiety, senility and Alzheimer's disease. ..
  18. 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. ..
  19. Regulation of PTH-induced Osteoanabolism by Inflammatory Lipids
    Yin Tintut; Fiscal Year: 2013
    ..receptor trafficking, downstream at the level of G-protein activation, or further downstream at the level of adenylate cyclase activation...
  20. C. trachomatis-mediated signaling pathways required for Type I IFN responses
    JEFFREY RYAN BARKER; Fiscal Year: 2013
    ..We plan to test this further by purifying the putative Chlamydia di-adenylate cyclase (DAC) protein CT012 and testing for conversion of radiolabeled ATP to c-di-AMP using thin layer ..
  21. 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. ..
  22. The role of Mc1r in melanocytic UV-induced DNA damage and repair responses
    JOHN A DORAZIO; Fiscal Year: 2013
    ..Together, these studies will lay the foundation for future translational studies designed to develop novel small molecule-based approaches for UV and cancer protection to prevent many cases of melanoma. ..
  23. Neurotrophins and Post-infarct Plasicity in Cardiac Sympathetic Neurons
    Beth A Habecker; Fiscal Year: 2013
    ..norepinephrine (NE) increases together with neuronal expression of the peptides galanin and PACAP (pituitary adenylate cyclase- activating polypeptides)...
  24. GABA-B-R-mediated prevention of pancreatic cancer
    Hildegard M Schuller; Fiscal Year: 2013
    ..Data generated will provide a preclinical basis for the use of GABA in the prevention of PDAC. ..
  25. Control of Oocyte Maturation in C. elegans
    DAVID IRWIN GREENSTEIN; Fiscal Year: 2013
    ..A major advance in the prior award period was our finding that G1s-adenylate cyclase signaling in the follicle-like sheath cells is required for all known MSP-dependent meiotic maturation ..
  26. Mechanisms of Antifibrotic Actions of Relaxin in the Liver
    Robert G Bennett; Fiscal Year: 2013
    ..The research proposed in this application may lead to targeted therapeutic strategies for the treatment of liver disease, a major health concern in the United States. ..
  27. Bordetella adenylate cyclase toxin: the role of cell interaction in toxin functio
    JOSHUA CLARK EBY; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The adenylate cyclase toxin (AC toxin) is necessary for disease caused by Bordetella pertussis, which has reemerged in the United States over the last two decades...
  28. The GABA-B receptor is a novel drug target for pancreatic cancer
    Hildegard M Schuller; Fiscal Year: 2012
    ..Since GABA and baclophen are already approved for the treatment of non-cancerous conditions in humans, results of this research can be rapidly translated into clinical trials. ..
  29. Genetic and estrogen-dependent regulation of the human PAC1R receptor and PTSD
    Kerry J Ressler; Fiscal Year: 2013
    ..Pituitary adenylate cyclase-activating polypeptide (PACAP) has previously been identified as a critical regulator of the stress response ..
  30. Regulation of Renal Response to Vasopressin by Glycogen Synthase
    Reena Rao; Fiscal Year: 2013
    ..In the GSK3[unreadable] knockout mice, adenylate cyclase activity and cAMP levels were reduced by an undetermined mechanism, which could have led to low aquaporin 2 ..
  31. Cyclic AMP Action During Sperm Function
    George L Gerton; Fiscal Year: 2012
    ..Understanding the role of SACY during spermatogenesis in the testis, sperm maturation in the epididymis, and sperm capacitation will allow us to improve the efficacy of sperm becoming fertilization-competent. ..
  32. RECOVERY OF FUNCTION FOLLOWING NEURAL DAMAGE
    Richard E Zigmond; Fiscal Year: 2010
    ..One of the genes that is elevated after nerve injury in sensory, motor, and sympathetic neurons is pituitary adenylate cyclase activating polypeptide (PACAP). PACAP stimulates cAMP synthesis and its own expression is elevated by cAMP...
  33. A Novel Function of the Oocyte in Estrogen-Regulated FSH Action
    Shunichi Shimasaki; Fiscal Year: 2009
    ..synergistic action of estrogen and oocytes occurs at a site downstream of the FSH receptor and upstream of adenylate cyclase. Further studies have provided the first evidence for a functional G protein-coupled receptor kinase (GRK)/?-..
  34. 5-HT1A receptor anti-apoptotic transduction pathways in suicide
    Victoria Arango; Fiscal Year: 2013
    ..We hope to gain insight into the neurobiology of suicide versus depression and identify novel drug targets for treatment of depression and prevention of suicide. ..
  35. Microtubule Stability in Lung Endothelium
    CRISTHIAAN D OCHOA ARENAS; Fiscal Year: 2012
    ....
  36. Calcium-Stimulated Adenylyl Cyclase Activity's Role in Stress-Facilitated Memory
    LINDSAY ANN WIECZOREK; Fiscal Year: 2010
    ..This work may eventually lead to the development of therapeutic interventions for people with abnormal memory changes from stress-related disorders as global, non- specific treatments can facilitate a host of unwanted side-effects. ..
  37. Circadian light entrainment following genetic ablation of retinal glutamate trans
    HEINRICH SELWYN GOMPF; Fiscal Year: 2010
    ..A number of possible co-transmitters, most notably pituitary adenylate cyclase activating peptide (PACAP), have been suspected to also play a role in mediating the light inputs and this ..
  38. Modulation of Oxidative phosphorylation by mitochondrial soluble adenylyl cyclase
    Giovanni Manfredi; Fiscal Year: 2013
    ..We will assess how sAC-cAMP-PKA modulation and protein phosphorylation in mitochondria from affected tissues and correlate it with disease progression. ..
  39. Eicosanoids and carbon monoxide in neonatal cerebral microcirculation
    ALIE JOSEPH KANU; Fiscal Year: 2012
    ..End of Abstract) ..
  40. Adenosine Receptors and Atherogenesis
    Katya Ravid; Fiscal Year: 2012
    ..Taken together, our proposed investigations should shed new light on the role of A2bARs in the pathogenesis of vascular dysfunction, and could focus attention on A2bAR activation as a therapeutic target. ..
  41. Structural Biology of G-Protein Coupled Receptors
    Wayne A Hendrickson; Fiscal Year: 2011
    ..GPCRs are actual and prospective pharmaceutical targets. ..
  42. Regulation of opioid receptor function in trigeminal ganglion
    William P Clarke; Fiscal Year: 2012
    ..The neurosecretion study of Drosophila as a model system provides extraordinary opportunities to use different methods of gene manipulation and of genomics with direct relevance to mammalian synaptic release and plasticity. ..
  43. Targeting compartmentalized phosphodiesterases to regulate CFTR function
    WITO H RICHTER; Fiscal Year: 2013
    ..This will allow us to trace the pools of cAMP that determine CFTR function, identify the key regulators in this compartment, and explore possible differences in cAMP signaling events between CF and non-CF epithelia. ..
  44. REGULATION OF THE SENSITIVITY OF DOPAMINE RECEPTORS
    KIM ARTHUR NEVE; Fiscal Year: 2013
    ..activation of mitogen-activated protein kinases, and D2 receptor-induced heterologous sensitization of adenylate cyclase will be determined in vitro and in vivo using dopamine receptor mutants deficient in arrestin binding...
  45. Transgenic Targeting of Vascular G Protein Signaling
    Karsten Peppel; Fiscal Year: 2010
    ..Data from these experiments should also increase our understanding of 21AR signaling in the setting of high blood pressure and help in the development of novel antihypertensive therapeutic strategies. ..
  46. GABAergic regulation of glutamine synthetase and its role in preventing epilepsy
    Stephen J Moss; Fiscal Year: 2013
    ..G-protein coupled receptors which couple to Gi/o, to modulate Ca transients, and inhibit the activity of adenylate cyclase. Preliminary studies have revealed that astrocytic GABABRs act to stabilize GS by reducing its ..
  47. Ligand Directed Functional Selectivity of G-Protein Coupled Receptor Signalling
    Gerry S Oxford; Fiscal Year: 2012
    ..As the receptors are important targets for pharmaco-therapies, the outcome of our research will guide the development of more refined and specific drugs for these disorders with fewer side effects. ..
  48. Mechanobiological Mechanism for Inflammaory Bone Loss
    Francis Young In Lee; Fiscal Year: 2013
    ..the functional interactions between pERK/cytokine expression and two diverging PTH signaling pathways (Gs/adenylate cyclase/cAMP and Gq/11-phospholipase C)...
  49. Role of Cyp2j-epoxygenases, sEH and PPARs in adenosine-induced vascular response
    Mohammed A Nayeem; Fiscal Year: 2013
    ..Such results can have a positive impact, as the identified components are expected to provide new targets to curb clinical problems linked with dysfunctional endothelium leading to hypertension. ..
  50. Role of adenylyl cyclase isoforms in collecting duct physiology &pathophysiology
    Donald E Kohan; Fiscal Year: 2013
    ....
  51. Adenylyl cyclase isoforms in collecting duct physiology and pathophysiology
    Donald E Kohan; Fiscal Year: 2013
    ....
  52. CELLULAR SUBSTRATES OF CEREBELLAR INFORMATION STORAGE
    David J Linden; Fiscal Year: 2010
    ..In addition, they have potential clinical relevance for both cerebellar motor disorders and disorders of learning and memory generally...
  53. Characterization of C02 Sensing and Regulatory Response in Borrelia burgdorferi
    Jennifer Hyde; Fiscal Year: 2013
    ..burgdorferi. In the proposed studies, the putative borrelial adenylate cyclase, cyaB, has been deleted and the CO2 regulation will be evaluated, as well as inhibition of cAMP accumulation,..
  54. Ca2+ Waves in Hepatocytes: Mechanisms and Effects
    Michael H Nathanson; Fiscal Year: 2013
    ....
  55. Mechanisms of Kinase-dependent Regulation of the V-ATPase in Kidney
    NURIA M PASTOR-SOLER; Fiscal Year: 2013
    ..The successful completion of the Aims of this application will contribute to new strategies to treat disorders of acidification in the kidney and in the urogenital tract. ..
  56. M. Tuberculosis Influences Host Matrix Metalloproteinases and Granuloma Formation
    NICOLE AMMERMAN; Fiscal Year: 2013
    ..Recently, our laboratory has characterized an M. tuberculosis-encoded adenylate cyclase (Rv0386) responsible for the production of 3', 5'-cyclic adenosine monophosphate (cAMP) that is ..
  57. 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. ..
  58. Biomarkers for Posttraumatic Stress in Women Following a Campus Mass Shooting
    Holly K Orcutt; Fiscal Year: 2012
    ..health history available prior to the mass shooting and predicts that fear physiology and the pituitary adenylate cyclase-activating polypeptide (PACAP) will mediate the relationship between a fateful, shared trauma and PTSS...
  59. Nociceptive Role of SST and NT receptor-expressing dorsal horn neurons
    RONALD GORDON WILEY; Fiscal Year: 2013
    ..These novel strategies for tonically exciting inhibitory interneurons with CTA,may open a new chapter in the search for safer, more effective ways to manage chronic, intractable pain. ..
  60. Role of the mAKAP Complex in Cardiac Hypertrophy
    MICHAEL SETH KAPILOFF; Fiscal Year: 2013
    ....
  61. Role of Drosophila circadian circuitry in experience-dependent sleep
    JEFFREY MICHAEL DONLEA; Fiscal Year: 2010
    ..I hypothesize that cells that have been previously identified as circadian oscillators are involved in the control of experience-dependent sleep. ..
  62. Retinal Neurons Afferent to the Circadian System
    GARY EDWARD PICKARD; Fiscal Year: 2010
    ..photosensitive retinal ganglion cells (ipRGCs) express melanopsin, a novel vertebrate opsin, and pituitary adenylate cyclase-activating peptide (PACAP)...
  63. REGULATION OF ALPHA-2 ADRENERGIC RECEPTORS
    David Bylund; Fiscal Year: 1993
    ..in the central nervous system, and alpha-2 adrenergic receptors, which are coupled to the inhibition of adenylate cyclase, are widely distributed...
  64. AUTONOMIC RECEPTOR FUNCTION IN LV HYPERTROPHY & FAILURE
    Dorothy Vatner; Fiscal Year: 1991
    ..her colleagues have identified several alterations in beta-adrenergic and muscarinic receptor function and adenylate cyclase activity in left ventricular hypertrophy and failure...
  65. TRANSEPITHELIAL TARGETING OF CHOLERA TOXIN
    Wayne Lencer; Fiscal Year: 1993
    ..the role of endocytosis and transepithelial transport in the Cholera toxin (CT) induced activation of adenylate cyclase in intestinal epithelial cells...
  66. G PROTEIN COUPLING IN ANTIDEPRESSANT DRUG ACTION
    Mark Rasenick; Fiscal Year: 2001
    ..Such knowledge should assist in the design of more efficient antidepressant drug therapy and may lead to a true understanding of the molecular basis of mood. ..
  67. ADENYLYL CYCLASE BY ADENOSINE 3'-PHOSPHATES
    Roger Johnson; Fiscal Year: 2003
    ....