title: Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A.
abstract: We report here the cloning, expression, and characterization of a dual-substrate, cAMP and cGMP, cyclic nucleotide phosphodiesterase (PDE) from mouse. This PDE contains the consensus sequence for a PDE catalytic domain, but shares <50% sequence identity with the catalytic domains of all other known PDEs and, therefore, represents a new PDE gene family, designated PDE10A. The cDNA for PDE10A is 3, 370 nt in length. It includes a full ORF, contains three in-frame stop codons upstream of the first methionine, and is predicted to encode a 779-aa enzyme. At the N terminus PDE10A has two GAF domains homologous to many signaling molecules, including PDE2, PDE5, and PDE6, which likely constitute a low-affinity binding site for cGMP. PDE10A hydrolyzes cAMP with a Km of 0.05 microM and cGMP with a Km of 3 microM. Although PDE10A has a lower Km for cAMP, the Vmax ratio (cGMP/cAMP) is 4.7. RNA distribution studies indicate that PDE10A is expressed at highest levels in testis and brain.
authors.affiliation: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Soderling
authors.forename: S J
authors.initials: SJ
authors.lastname: Bayuga
authors.forename: J A
authors.initials: JA
authors.lastname: Beavo
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D000242:Cyclic AMP; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP