A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs.
We have isolated cDNAs for four human genes (DPDE1 through DPDE4) closely related to the dnc learning and memory locus of Drosophila melanogaster. The deduced amino acid sequences of the Drosophila and human proteins have considerable homology, extending beyond the putative catalytic region to include two novel, highly conserved, upstream conserved regions (UCR1 and UCR2). The upstream conserved regions are located in the amino-terminal regions of the proteins and appear to be unique to these genes. Polymerase chain reaction analysis suggested that these genes encoded the only homologs of dnc in the human genome. Three of the four genes were expressed in Saccharomyces cerevisiae and shown to encode cyclic AMP-specific phosphodiesterases. The products of the expressed genes displayed the pattern of sensitivity to inhibitors expected for members of the type IV, cyclic AMP-specific class of phosphodiesterases. Each of the four genes demonstrated a distinctive pattern of expression in RNA from human cell lines.
Bolger
G
G
Cold Spring Harbor Laboratory, New York 11724.
Michaeli
T
T
Martins
T
T
St John
T
T
Steiner
B
B
Rodgers
L
L
Riggs
M
M
Wigler
M
M
Ferguson
K
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004247:DNA; D004331:Drosophila melanogaster; D006801:Humans; D007858:Learning; D008568:Memory; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017385:Sequence Homology; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D000928:Antidepressive Agents; D004247:DNA; D015105:3',5'-Cyclic-AMP Phosphodiesterases