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

Soderling SH,Bayuga SJ,Beavo JA

doi

10.1073/pnas.96.12.7071

keywords:

subject

Has Abstract

pub_date

1999-06-08 00:00:00

pages

7071-6

issue

12

eissn

0027-8424

issn

1091-6490

journal_volume

96

pub_type

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