EXPRESSION, STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE HUMAN CGMP-BINDING CGMP-SPECIFIC PHOSPHODIESTERASE PDE5A GENE

cGMP-binding, cGMP-specific phosphodiesterase which is encoded by the PDE5A gene plays important roles in cardiovascular system, and is a si gnificant target molecule of therapeutic agents. However, little is kn own about molecular characteristics of the human PDE5A gene. The 4.4-k b cDNA encoding human PDE5A was isolated from lung and placenta cDNA l ibraries. The deduced amino acid sequence analysis demonstrated that N -terminal amino acid sequence is dissimilar to that of rat PDE5A [Kote ra, J., Yanaka, N., Fujishige, K., Imai, Y., Akatsuka, H., Ishizuka, T ., Kawashima, K. & Omori, K. (1997) Eur J. Biochem. 249, 434-442]. Hum an PDE5A mRNA is produced in high amounts in various tissues such as p ancreas, skeletal muscle, placenta, heart, thyroid, adrenal cortex, te stis, small intestine and stomach. In addition, the megakaryocyte-like cell line Dami cells and two types of human vascular smooth muscle ce lls also produce the mRNA. Over 100-kb chromosomal DNA corresponding t o the human PDE5A gene was isolated and analyzed. The human PDE5A gene was revealed to contain 21 exons. Comparison of genomic organization with the rod photoreceptor phosphodiesterase beta-subunit gene (PDE6B) , which is another kind of cGMP-specific phosphodiesterase, has shown that the PDE5A and PDE6B genes are very similar in their relative exon -intron organization. In particular, the evolutionary relatedness of t hese genes was suggested in the catalytic domain. Furthermore, chromos omal location of the PDE5A gene was defined as being chromosome 4q26 b y fluorescent ill situ hybridization analysis.