Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Soderling, SH; Bayuga, SJ; Beavo, JA

Published Date

  • June 8, 1999

Published In

Volume / Issue

  • 96 / 12

Start / End Page

  • 7071 - 7076

PubMed ID

  • 10359840

Pubmed Central ID

  • PMC22059

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.12.7071


  • eng

Conference Location

  • United States