Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases.
We have reported alternative splice variants of cGMP-binding cGMP-specific phosphodiesterases (PDE5A), i.e. rat PDE5A2, human PDE5A1, canine PDE5A1 and PDE5A2, which possess distinct N-terminal sequences. In this study, the DNA sequences corresponding to the unique N-terminal portions of PDE5A1 and PDE5A2 were shown to be tandemly located upstream of exons encoding the common region of PDE5A in both human and rat PDE5A genes. The presence of human PDE5A2 and rat PDE5A1 transcripts in lung was confirmed by reverse transcriptase-PCR. These results indicated that two variant forms of PDE5A exist in humans, canines and rats. We examined the tissue distribution of the two variants of human PDE5A in adult and fetal humans. The patterns of expression of the two alternatively spliced transcripts of human PDE5A in human tissues differed. Many putative regulatory elements including cAMP response elements were observed in the 5'-untranslated region and intron of the PDE5A gene. The levels of the PDE5A transcripts, especially the PDE5A2 transcripts, were increased by a cAMP analogue in cultured rat vascular smooth muscle cells, indicating that the PDE5A2 is an inducible variant of PDE5A in rats.
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd. Saitama, Japan.
J
J
Kotera
K
K
Fujishige
Y
Y
Imai
E
E
Kawai
H
H
Michibata
H
H
Akatsuka
N
N
Yanaka
K
K
Omori
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004285:Dogs; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C022994:cyclic GMP-binding protein; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; C517384:Pde5a protein, rat; D006152:Cyclic GMP