Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase

A member of the phosphodiesterase (PDE)7 family with high affinity and spec ificity for cAMP has been identified. Based on sequence homologies, we desi gnate this PDE as PDE7B. The full-length cDNA of PDE7B is 2399 bp, and its ORF sequence predicts a protein of 446 amino acids with a molecular mass of 50.1 kDa. Comparison of the predicted protein sequences of PDE7A and PDE7B reveals an identity of 70% in the catalytic domain. Northern blotting indi cates that the mRNA of PDE7B is 5.6 kb. It is most highly expressed in panc reas followed by brain, heart, thyroid, skeletal muscle, eye, ovary, submax illary gland, epididymus, and liver. Recombinant PDE7B protein expressed in a Baculovirus expression system is specific for cAMP with a K-m of 0.03 mu M. Within a series of common PDE inhibitors, it is most potently inhibited by 3-isobutyl-1-methylxanthine with an IC50 of 2.1 mu M. It is also inhibi ted by papaverine, dipyridamole, and SCH51866 at higher doses. PDE7A and PD E7B exhibit the same general pattern of inhibitor specificity among the sev eral drugs tested. However, differences in IC50 for some of the drugs sugge st that isozyme selective inhibitors can be developed.