adenylyl cyclases


Summary: Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP.

Top Publications

  1. Rich T, Fagan K, Nakata H, Schaack J, Cooper D, Karpen J. Cyclic nucleotide-gated channels colocalize with adenylyl cyclase in regions of restricted cAMP diffusion. J Gen Physiol. 2000;116:147-61 pubmed
    ..Localized cAMP signals should also facilitate the differential regulation of cellular targets. ..
  2. Rybin V, Xu X, Lisanti M, Steinberg S. Differential targeting of beta -adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway. J Biol Chem. 2000;275:41447-57 pubmed
  3. Huang Y, Kandel E. D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc Natl Acad Sci U S A. 1995;92:2446-50 pubmed
  4. Chen F, Bilezikjian L, Perrin M, Rivier J, Vale W. Corticotropin releasing factor receptor-mediated stimulation of adenylate cyclase activity in the rat brain. Brain Res. 1986;381:49-57 pubmed
    ..These results suggest that, as in the anterior pituitary, at least some of the physiological responses mediated by CRF receptors in the brain utilize the cyclic nucleotide regulatory pathway as a post-receptor mechanism. ..
  5. Wolter S, Dittmar F, Seifert R. cCMP and cUMP in Apoptosis: Concepts and Methods. Handb Exp Pharmacol. 2017;238:25-47 pubmed publisher
  6. Vatner S, Vatner D, Yan L. Models of longevity (calorie restriction and AC5 KO): result of three bad hypotheses. Aging (Albany NY). 2012;4:662-3 pubmed
  7. Liebmann C, Graness A, Boehmer A, Kovalenko M, Adomeit A, Steinmetzer T, et al. Tyrosine phosphorylation of GSalpha and inhibition of bradykinin-induced activation of the cyclic AMP pathway in A431 cells by epidermal growth factor receptor. J Biol Chem. 1996;271:31098-105 pubmed
    ..We propose that Gsalpha may represent a key regulatory protein in the cross-talk between the signal transduction pathways of BK and EGF in A431 cells. ..
  8. Onodera Y, Nam J, Bissell M. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways. J Clin Invest. 2014;124:367-84 pubmed publisher
    ..Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. ..
  9. Barouki R, Chobert M, Billon M, Finidori J, Tsapis R, Hanoune J. Glucocorticoid hormones increase the activity of gamma-glutamyltransferase in a highly differentiated hepatoma cell line. Biochim Biophys Acta. 1982;721:11-21 pubmed
    ..These results suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of glucocorticoid effects on differentiated cells. ..

More Information


  1. Li Q, Cui M, Yang F, Li N, Jiang B, Yu Z, et al. A cullin 4B-RING E3 ligase complex fine-tunes pancreatic ? cell paracrine interactions. J Clin Invest. 2017;127:2631-2646 pubmed publisher
    ..Our results reveal an epigenetic regulatory mechanism of ? cell paracrine interactions in which CRL4B-PRC2 complexes, Cav1.2, and AC6 expression fine-tune somatostatin secretion and facilitate glucose homeostasis in pancreatic islets. ..
  2. Roman T, Cannon M, Vadlamudi S, Buchkovich M, Wolford B, Welch R, et al. A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus. Diabetes. 2017;66:2521-2530 pubmed publisher
    ..Together, these data suggest that rs11708067-A risk allele contributes to type 2 diabetes by disrupting an islet enhancer, which results in reduced ADCY5 expression and impaired insulin secretion. ..
  3. Yanda M, Liu Q, Cebotaru L. An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst growth in polycystic kidney disease. Am J Physiol Renal Physiol. 2017;313:F997-F1004 pubmed publisher
    ..We found that ACY-1215 lowered cAMP levels and protein expression of adenylyl cyclase 6. Our results suggest that HDAC6 could potentially serve as a therapeutic target in ADPKD. ..
  4. Aono R, Yamasaki M, Tamura G. High and selective resistance to mecillinam in adenylate cyclase-deficient or cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli. J Bacteriol. 1979;137:839-45 pubmed
    ..In the absence of cAMP, cya strains neither stopped dividing nor lysed; they were resistant to the second, lethal effect of mecillinam. ..
  5. Sakai M, Suzuki T, Tomita K, Yamashita S, Palikhe S, Hattori K, et al. Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation. Am J Physiol Heart Circ Physiol. 2017;312:H1224-H1237 pubmed publisher
  6. Schobesberger S, Wright P, Tokar S, Bhargava A, Mansfield C, Glukhov A, et al. T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure. Cardiovasc Res. 2017;113:770-782 pubmed publisher
    ..Complete disorganization of β2AR-mediated cAMP signalling due to changes in functional receptor localization and cellular structure occurs at 16-week post-MI. ..
  7. Navarro G, Aguinaga D, Moreno E, Hradsky J, Reddy P, Cortés A, et al. Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers. Chem Biol. 2014;21:1546-56 pubmed publisher
  8. Zhou R, Wang J, You Y, Sun J, Song Y, Yuan H, et al. [Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19:576-582 pubmed
    ..The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway. ..
  9. Hardwick J, Clason T, Tompkins J, Girard B, Baran C, Merriam L, et al. Recruitment of endosomal signaling mediates the forskolin modulation of guinea pig cardiac neuron excitability. Am J Physiol Cell Physiol. 2017;313:C219-C227 pubmed publisher
  10. Gao M, Lai N, Giamouridis D, Kim Y, Guo T, Hammond H. Cardiac-directed expression of a catalytically inactive adenylyl cyclase 6 protects the heart from sustained β-adrenergic stimulation. PLoS ONE. 2017;12:e0181282 pubmed publisher
    ..0001). Mice with cardiac-directed AC6mut expression weathered the deleterious effects of continuous isoproterenol infusion better than control mice, indicating cardiac protection. ..
  11. Gros R, Benovic J, Tan C, Feldman R. G-protein-coupled receptor kinase activity is increased in hypertension. J Clin Invest. 1997;99:2087-93 pubmed
    ..The increase in GRK activity may underlie the reduction in beta-adrenergic responsiveness characteristic of the hypertensive state. ..
  12. Atkinson J, Sullivan T, Kelly J, Parker C. Stimulation by alcohols of cyclic AMP metabolism in human leukocytes. Possible role of cyclic AMP in the anti-inflammatory effects of ethanol. J Clin Invest. 1977;60:284-94 pubmed
    ..Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP. ..
  13. Karimova G, Pidoux J, Ullmann A, Ladant D. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A. 1998;95:5752-6 pubmed
  14. Hollingsworth E, McNeal E, Burton J, Williams R, Daly J, Creveling C. Biochemical characterization of a filtered synaptoneurosome preparation from guinea pig cerebral cortex: cyclic adenosine 3':5'-monophosphate-generating systems, receptors, and enzymes. J Neurosci. 1985;5:2240-53 pubmed
    ..There is no apparent change in the density of many receptors or ion channels. Levels of A1-adenosine and H1-histamine receptors are increased, whereas levels of so-called peripheral benzodiazepine-binding sites are decreased. ..
  15. Richlitzki A, Latour P, Schwärzel M. Null EPAC mutants reveal a sequential order of versatile cAMP effects during Drosophila aversive odor learning. Learn Mem. 2017;24:210-215 pubmed publisher
    ..Thereby we show that versatile cAMP-dependent mechanisms are engaged within a sequential order that correlate to individual trials of the training session. ..
  16. Polimanti R, Zhang H, Smith A, Zhao H, Farrer L, Kranzler H, et al. Genome-wide association study of body mass index in subjects with alcohol dependence. Addict Biol. 2017;22:535-549 pubmed publisher
    ..These loci offer molecular insights regarding the regulatory mechanisms of body mass in the context of AD. ..
  17. Carvalho de Freitas R, Lonien S, Malvezi A, Silveira G, Wowk P, da Silva R, et al. Trypanosoma cruzi: Inhibition of infection of human monocytes by aspirin. Exp Parasitol. 2017;182:26-33 pubmed publisher
    ..Altogether, these results reinforce the idea that the cyclooxygenase pathway plays a fundamental role in the process of parasite invasion in an in vitro model of T. cruzi infection. ..
  18. Paccani S, Benagiano M, Savino M, Finetti F, Tonello F, D Elios M, et al. The adenylate cyclase toxin of Bacillus anthracis is a potent promoter of T(H)17 cell development. J Allergy Clin Immunol. 2011;127:1635-7 pubmed publisher
  19. Upadhyaya N, Mago R, Staskawicz B, Ayliffe M, Ellis J, Dodds P. A bacterial type III secretion assay for delivery of fungal effector proteins into wheat. Mol Plant Microbe Interact. 2014;27:255-64 pubmed publisher
    ..Thus, the modified AvrRpm1:effector-Pseudomonas fluorescens system is an effective tool for large-scale screening of pathogen effectors for recognition in wheat. ..
  20. Guichard A, Jain P, Moayeri M, Schwartz R, Chin S, Zhu L, et al. Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport. PLoS Pathog. 2017;13:e1006603 pubmed publisher
  21. Zhang G, Feenstra B, Bacelis J, Liu X, Muglia L, Juodakis J, et al. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. N Engl J Med. 2017;377:1156-1167 pubmed publisher
    ..Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement. (Funded by the March of Dimes and others.). ..
  22. Bouhelal R, Smounya L, Bockaert J. 5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol. 1988;151:189-96 pubmed
    ..Our conclusion is that, in addition to the 5-HT1A receptor, the 5-HT1B receptor is also negatively coupled to adenylate cyclase. ..
  23. Brodde O, Konschak U, Becker K, Rüter F, Poller U, Jakubetz J, et al. Cardiac muscarinic receptors decrease with age. In vitro and in vivo studies. J Clin Invest. 1998;101:471-8 pubmed
  24. Rudkin J, McLoughlin R, Preston A, Massey R. Bacterial toxins: Offensive, defensive, or something else altogether?. PLoS Pathog. 2017;13:e1006452 pubmed publisher
  25. van Keulen S, Rothlisberger U. Exploring the inhibition mechanism of adenylyl cyclase type 5 by n-terminal myristoylated G?i1. PLoS Comput Biol. 2017;13:e1005673 pubmed publisher
  26. BOSSE K, Oginsky M, Susick L, Ramalingam S, Ferrario C, Conti A. Adenylyl Cyclase 1 Is Required for Ethanol-Induced Locomotor Sensitization and Associated Increases in NMDA Receptor Phosphorylation and Function in the Dorsal Medial Striatum. J Pharmacol Exp Ther. 2017;363:148-155 pubmed publisher
    ..Together, these data support a critical and specific role for AC1 in striatal signaling that mediates ethanol-induced behavioral sensitization, and identify GluN2B-containing NMDARs as an important AC1 target. ..
  27. Richardson T, Zheng J, Davey Smith G, Timpson N, Gaunt T, Relton C, et al. Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk. Am J Hum Genet. 2017;101:590-602 pubmed publisher
    ..Integrating our results with expression quantitative trait loci data, we provide evidence that variation at these regulatory regions is likely to also influence gene expression levels at these loci. ..
  28. Paz M, Ramos M, Ramirez G, Souza D. Differential effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity in chick optic tectum. FEBS Lett. 1994;355:205-8 pubmed
  29. Huffaker T, Corcoran T, Wagner J. Adenosine inhibits cell division and promotes neurite extension in PC12 cells. J Cell Physiol. 1984;120:188-96 pubmed
    ..Adenosine also increases the rate of neurite formation of both long and short neurites in response to NGF. ..
  30. Ori D, Murase M, Kawai T. Cytosolic nucleic acid sensors and innate immune regulation. Int Rev Immunol. 2017;36:74-88 pubmed publisher
    ..In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors...
  31. Abe A, Nishimura R, Kuwae A. Bordetella effector BopN is translocated into host cells via its N-terminal residues. Microbiol Immunol. 2017;61:206-214 pubmed publisher
    ..Furthermore, BopN appears to play an auxiliary role in BteA-mediated cytotoxicity. Thus, BopN can apparently translocate into host cells and may facilitate activity of BteA. ..
  32. Wilkins P, Suchovsky D, Berti Mattera L. Immortalized schwann cells express endothelin receptors coupled to adenylyl cyclase and phospholipase C. Neurochem Res. 1997;22:409-18 pubmed
    ..The actions of ETs on Schwann cells provide a novel example of the influence of vascular factors on nerve function. ..
  33. Douglas A, Andreoletti G, Talbot K, Hammans S, Singh J, Whitney A, et al. ADCY5-related dyskinesia presenting as familial myoclonus-dystonia. Neurogenetics. 2017;18:111-117 pubmed publisher
    ..ADCY5-related dyskinesia may manifest variable expressivity within a single family, and affected individuals may be initially diagnosed with differing neurological phenotypes. ..
  34. Botsford J, Harman J. Cyclic AMP in prokaryotes. Microbiol Rev. 1992;56:100-22 pubmed
    ..Often the only data that support cAMP involvement in these processes includes cAMP measurement, detection of the enzymes involved in cAMP metabolism, or observed effects of high concentrations of the nucleotide on cell growth. ..
  35. Matsumoto K, Uno I, Ishikawa T. Genetic analysis of the role of cAMP in yeast. Yeast. 1985;1:15-24 pubmed
  36. Huang Y. [Progress in studies on the genetic risk factors for nonsyndromic cleft lip or palate in China]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2017;52:223-228 pubmed publisher
    ..3??????????????????????????????rs8049367??????????????????????????????????????????????????????????????????. ..
  37. Souza D, Ramirez G. Effects of guanine nucleotides on kainic acid binding and on adenylate cyclase in chick optic tectum and cerebellum. J Mol Neurosci. 1991;3:39-45 pubmed
  38. Kruglov E, Ananthanarayanan M, Sousa P, Weerachayaphorn J, Guerra M, Nathanson M. Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP. Biochem Biophys Res Commun. 2017;486:659-664 pubmed publisher
    ..The findings furthermore suggest that this mechanism is relevant for hormonal regulation of bile secretion. ..
  39. Shahidullah M, Mandal A, Delamere N. A Role for Calcium-Activated Adenylate Cyclase and Protein Kinase A in the Lens Src Family Kinase and Na,K-ATPase Response to Hyposmotic Stress. Invest Ophthalmol Vis Sci. 2017;58:4447-4456 pubmed publisher
    ..8-pCPT-cAMP caused robust SFK activation. Using Western blot, two calcium-activated adenylyl cyclases, ADCY3 and ADCY8, were detected in lens epithelium...
  40. Turku A, Rinne M, Boije af Gennäs G, Xhaard H, Lindholm D, Kukkonen J. Orexin receptor agonist Yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity. PLoS ONE. 2017;12:e0178526 pubmed publisher
    ..Thus, Yan 7874 is a weak partial agonist of orexin receptors. It also displays strong off-target effects in the same concentration range, culminating in necrotic cell demise. This makes Yan 7874 unsuitable as orexin receptor agonist. ..
  41. Friedman J, Méneret A, Chen D, Trouillard O, Vidailhet M, Raskind W, et al. ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias. Mov Disord. 2016;31:147-8 pubmed publisher
  42. Wardzala L, Jeanrenaud B. Potential mechanism of insulin action on glucose transport in the isolated rat diaphragm. Apparent translocation of intracellular transport units to the plasma membrane. J Biol Chem. 1981;256:7090-3 pubmed
    ..W., and Wardzala, L. J. (1980) J. Biol. Chem. 255, 4758-4762) and suggest that this mechanism of insulin-stimulated glucose transport activity may be general to other cell types. ..
  43. Stanton P, Sarvey J. Depletion of norepinephrine, but not serotonin, reduces long-term potentiation in the dentate gyrus of rat hippocampal slices. J Neurosci. 1985;5:2169-76 pubmed
    ..These results suggest that endogenous hippocampal NE is more important to LTP in the dentate than is endogenous 5-HT. ..
  44. Liu J, Robinson P, Funder J, Engler D. A comparative study of the role of adenylate cyclase in the release of adrenocorticotropin from the ovine and rat anterior pituitary. Mol Cell Endocrinol. 1994;101:173-81 pubmed
  45. Rodbell M, Birnbaumer L, Pohl S, Krans H. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanylnucleotides in glucagon action. J Biol Chem. 1971;246:1877-82 pubmed