title: [Phosphodiesterase 3 mediates cross-talk between the protein kinase- and cGMP- dependent pathways and cyclic AMP metabolism].
abstract: PDE3 is a dual-substrate phosphodiesterase responsible for hydrolyzing both cAMP and cGMP whilst being simultaneously inhibited by cGMP. This feature is related to presence of the 44 amino acid insert in the catalytic domain, which determines the mechanism of introduction of the cyclic nucleotide into the catalytic pocket of the enzyme. Once bound in the catalytic site cGMP results in steric hindrance for cAMP to enter the site. The regulatory domain of PDE3 consists of two hydrophobic regions: NHR1 and NHR2. Their presence defines the enzyme's intracellular localization, thus determining its participation in particular signaling cascades. Due to the properties of PDE3 this enzyme has exceptional importance for the cross-talk between cAMP-dependent signaling and other cascades. There are two different mechanisms of action of PDE3 enzymes in cell signaling pathways. In many signaling cascades assembly of a signalosome is necessary for phosphorylation and activation of the PDE3 proteins. In response to certain hormones and growth factors, PDE3 merges the metabolism of cAMP with protein kinase-dependent signaling pathways. PDE3 also controls the level of cAMP with regard to the alternating concentration of cGMP. This effect occurs in signaling cascades activated by natriuretic peptide.
authors.affiliation: Laboratorium Białek Sygnałowych, Instytut Immunologii i Terapii Doświadczalnej PAN im. L. Hirszfelda we Wrocławiu.
authors.forename: Edyta
authors.initials: E
authors.lastname: Makuch
authors.forename: Janusz
authors.initials: J
authors.lastname: Matuszyk
mesh_terms: D020134:Catalytic Domain; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D057927:Hydrophobic and Hydrophilic Interactions; D045265:Natriuretic Peptides / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D011494:Protein Kinases / Q000378:metabolism*; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D045265:Natriuretic Peptides; D020033:Protein Isoforms; D000242:Cyclic AMP; D011494:Protein Kinases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D006152:Cyclic GMP