Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3′,5′-cyclic nucleotide phosphodiesterase

• Published in: Gene 1997-05, Vol.191 (1), p.89-95
• Main Authors: Rosman, Guy J, Martins, Timothy J, Sonnenburg, William K, Beavo, Joseph A, Ferguson, Ken, Loughney, Kate
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - genetics; 3',5'-Cyclic-GMP Phosphodiesterases - metabolism; 5′-Splice variants; Amino Acid Sequence; Animals; Base Sequence; Cattle; Cyclic GMP - metabolism; DNA, Complementary; EHNA; Enzyme Activation; Humans; Molecular Sequence Data; PDE2A; Rats; RNA, Messenger - metabolism; Sequence Homology, Amino Acid
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/S0378-1119(97)00046-2

Human cyclic GMP-stimulated 3′,5′-cyclic nucleotide phosphodiesterase (PDE2A3) cDNAs were cloned from hippocampus and fetal brain cDNA libraries. A 4.2-kb composite DNA sequence constructed from overlapping cDNA clones encodes a 941 amino acid protein with a predicted molecular mass of 105 715 Da. Extracts prepared from yeast expressing the human PDE2A3 hydrolyzed both cyclic AMP (cAMP) and cyclic GMP (cGMP). This activity was inhibited by EHNA, a selective PDE2 inhibitor, and was stimulated three-fold by cGMP. Human PDE2A is expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas. The human PDE2A3 differs from the bovine PDE2A1 and rat PDE2A2 proteins at the amino terminus but its amino-terminal sequence is identical to the bovine PDE2A3 sequence. The different amino termini probably arise from alternative exon splicing of the PDE2A mRNA.