We report here the cloning, expression, and characterization of a dual-subs
trate, cAMP and cGMP, cyclic nucleotide phosphodiesterase (PDE) from mouse.
This PDE contains the consensus sequence for a PDE catalytic domain, but s
hares <50% sequence identity with the catalytic domains of all other known
PDEs and, therefore, represents a new PDE gene family, designated PDE10A, T
he 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 predict
ed to encode a 779-aa enzyme. At the N terminus PDE10A has two GAF domains
homologous to many signaling molecules, including PDE2, PDES, and PDE6, whi
ch likely constitute a low-affinity binding site for cGMP, PDE10A hydrolyze
s cAMP with a K-m of 0.05 mu M and cGMP with a K-m of 3 mu M. Although PDE1
0A has a lower K-m for cAMP, the V-max ratio (cGMP/cAMP) is 4.7, RNA distri
bution studies indicate that PDE10A is expressed at highest levels in testi
s and brain.