Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene

Authors


  • Correspondence to K. Omori, Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd, 16−89 Kashima-3-chome, Yodogawa-ku, Osaka, Japan 532-8505

  • Fax: +81 6 300 2593.

  • E-mail:k-omori@tanabe.co.jp

  • Abbreviations. PDE, 3′,5′-cyclic nucleotide phosphodiesterase; PDE5A, cGMP-binding cGMP-specific PDE; cGMP-PDE6B, β-subunit of rod photoreceptor phosphodiesterase; SMC, smooth muscle cell; FISH, fluorescent in situ hybridization; FITC, fluorescein isothiocyanate.

  • Enzyme. Cyclic-nucleotide phosphodiesterase ( EC3.1.4.17).

  • Note 1. First and second authors contributed equally to this work.

  • Note 2. The nucleotide sequence data published here have been submitted to the sequence data bank and are available under accession nos D89094, and AB001615AB001635.

Abstract

cGMP-binding, cGMP-specific phosphodiesterase which is encoded by the PDE5A gene plays important roles in cardiovascular system, and is a significant target molecule of therapeutic agents. However, little is known about molecular characteristics of the human PDE5A gene. The 4.4-kb cDNA encoding human PDE5A was isolated from lung and placenta cDNA libraries. The deduced amino acid sequence analysis demonstrated that N-terminal amino acid sequence is dissimilar to that of rat PDE5A [Kotera, J., Yanaka, N., Fujishige, K., Imai, Y., Akatsuka, H., Ishizuka, T., Kawashima, K. & Omori, K. (1997) Eur. J. Biochem. 249, 434−442]. Human PDE5A mRNA is produced in high amounts in various tissues such as pancreas, skeletal muscle, placenta, heart, thyroid, adrenal cortex, testis, small intestine and stomach. In addition, the megakaryocyte-like cell line Dami cells and two types of human vascular smooth muscle cells also produce the mRNA. Over 100-kb chromosomal DNA corresponding to 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 β-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 these genes was suggested in the catalytic domain. Furthermore, chromosomal location of the PDE5A gene was defined as being chromosome 4q26 by fluorescent in situ hybridization analysis.

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