Overview of PDEs and their regulation.
Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleotide concentrations, which are determined by a balance in production and degradation of cAMP and cGMP. Degradation of cyclic nucleotides is catalyzed by 3',5'-cyclic nucleotide phosphodiesterases (PDEs), and therefore regulation of PDEs hydrolytic activity is important for modulation of cellular functions. Mammalian PDEs are composed of 21 genes and are categorized into 11 families based on sequence homology, enzymatic properties, and sensitivity to inhibitors. PDE families contain many splice variants that mostly are unique in tissue-expression patterns, gene regulation, enzymatic regulation by phosphorylation and regulatory proteins, subcellular localization, and interaction with association proteins. Each unique variant is closely related to the regulation of a specific cellular signaling. Thus, multiple PDEs function as a particular modulator of each cardiovascular function and regulate physiological homeostasis.
Omori
Kenji
K
Discovery Research Laboratories, Tanabe Seiyaku Co Ltd, 2-50 Kawagishi 2-chome, Toda, Saitama 335-8505, Japan. k-omori@tanabe.co.jp
Kotera
Jun
J
D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008322:Mammals / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D032342:Muscle Cells / Q000201:enzymology / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000502:physiology; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000145:classification / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D010802:Phylogeny; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000201:enzymology
D007527:Isoenzymes; D010750:Phosphoproteins; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP