title: Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic purine and pyrimidine nucleotides.
abstract: The cyclic purine nucleotides cAMP and cGMP are well-characterized second messengers and activators of PKA and PKG, respectively. In contrast, the functions of the cyclic pyrimidine nucleotides cCMP and cUMP are poorly understood. cCMP induces relaxation of smooth muscle via PKGI, and phosphodiesterases differentially hydrolyze cNMPs. Here, we report that cNMPs differentially activate PKA isoforms and PKGIα. The combination of cCMP with cAMP reduced the EC(50) of cAMP for PKA. PKGIα exhibited higher specificity for the cognate cNMP than PKA. Our data support a role of cCMP and cUMP as second messengers.
authors.affiliation: Institute of Pharmacology, Medical School of Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wolter
authors.forename: Marina
authors.initials: M
authors.lastname: Golombek
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D000242:Cyclic AMP / Q000737:chemistry*; D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit / Q000737:chemistry*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000737:chemistry*; D006152:Cyclic GMP / Q000737:chemistry*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry*; D004789:Enzyme Activation; D009712:Nucleotides, Cyclic / Q000737:chemistry*; D014542:Uridine Monophosphate / Q000737:chemistry*
chemical_list: D054754:Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D009712:Nucleotides, Cyclic; C045338:cyclic 3',5'-uridine monophosphate; D000242:Cyclic AMP; D014542:Uridine Monophosphate; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP