title: ExoY from Pseudomonas aeruginosa is a nucleotidyl cyclase with preference for cGMP and cUMP formation.
abstract: In addition to the well known second messengers cAMP and cGMP, mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. Soluble guanylyl cyclase and soluble adenylyl cyclase produce all four cNMPs. Several bacterial toxins exploit mammalian cyclic nucleotide signaling. The type III secretion protein ExoY from Pseudomonas aeruginosa induces severe lung damage and effectively produces cGMP. Here, we show that transfection of mammalian cells with ExoY or infection with ExoY-expressing P. aeruginosa not only massively increases cGMP but also cUMP levels. In contrast, the structurally related CyaA from Bordetella pertussis and edema factor from Bacillus anthracis exhibit a striking preference for cAMP increases. Thus, ExoY is a nucleotidyl cyclase with preference for cGMP and cUMP production. The differential effects of bacterial toxins on cNMP levels suggest that cUMP plays a distinct second messenger role.
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: beckert-ulrike81@email.de.
authors: Urike
authors: U
authors: Beckert
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: wolter.sabine@mh-hannover.de.
authors: Sabine
authors: S
authors: Wolter
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: hartwig.christina@mh-hannover.de.
authors: Christina
authors: C
authors: Hartwig
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: baehre.heike@mh-hannover.de.
authors: Heike
authors: H
authors: Bähre
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Core Unit Metabolomics, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: kaever.volkhard@mh-hannover.de.
authors: Volkhard
authors: V
authors: Kaever
authors: Institut Pasteur, CNRS UMR 3528, Department of Structural Biology and Chemistry, 25-28 rue du Docteur Roux, F-75015 Paris, France. Electronic address: daniel.ladant@pasteur.fr.
authors: Daniel
authors: D
authors: Ladant
authors: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Electronic address: frankd@mcw.edu.
authors: Dara W
authors: DW
authors: Frank
authors: Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.
authors: Roland
authors: R
authors: Seifert
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D002470:Cell Survival; D006152:Cyclic GMP / Q000096:biosynthesis*; D005964:Glucosyltransferases / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000096:biosynthesis*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D009712:Nucleotides, Cyclic; C045338:cyclic 3',5'-uridine monophosphate; D014542:Uridine Monophosphate; C111504:ExoY protein, bacteria; D005964:Glucosyltransferases; D009713:Nucleotidyltransferases; D006152:Cyclic GMP
keywords: Cyclic AMP; Cyclic CMP; Cyclic GMP; Cyclic UMP; Pseudomonas aeruginosa