| http://purl.uniprot.org/citations/12554648 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12554648 | http://www.w3.org/2000/01/rdf-schema#comment | "cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival. PDE5 contains two N-terminal domains (GAF A and GAF B), but the functional roles of these domains have not been determined. Here we show that recombinant PDE5 is activated directly upon cGMP binding to the GAF A domain, and this effect does not require PDE5 phosphorylation. PDE5 exhibited time- and concentration-dependent reversible activation in response to cGMP, with the highest activation (9-to 11-fold) observed at low substrate concentrations (0.1 micro M cGMP). A monoclonal antibody directed against GAF A blocked cGMP binding, prevented PDE5 activation and decreased basal activity, revealing that PDE5 in its non-activated state has low intrinsic catalytic activity. Activated PDE5 showed higher sensitivity towards sildenafil than non-activated PDE5. The stimulatory effect of cGMP binding on the catalytic activity of PDE5 suggests that this mechanism of enzyme activation may be common among other GAF domain-containing proteins. The data also suggest that development of agonists and antagonists of PDE5 activity based on binding to this site might be possible."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.org/dc/terms/identifier | "doi:10.1093/emboj/cdg051"xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/author | "Tang X.B."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/author | "Beavo J.A."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/author | "Rybalkin S.D."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/author | "Rybalkina I.G."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/author | "Shimizu-Albergine M."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/name | "EMBO J"xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/pages | "469-478"xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/title | "PDE5 is converted to an activated state upon cGMP binding to the GAF A domain."xsd:string |
| http://purl.uniprot.org/citations/12554648 | http://purl.uniprot.org/core/volume | "22"xsd:string |
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