cDNA cloning and gene expression of human type Iα cGMP-dependent protein kinase

Naohisa Tamura, Hiroshi Itoh, Yoshihiro Ogawa, Osamu Nakagawa, Masaki Harada, Tae Hwa Chun, Shin Ichi Suga, Takaaki Yoshimasa, Kazuwa Nakao

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Abstract

The type I cGMP-dependent protein kinase (cGK) is one of the major pathways for the cGMP cascade and has been demonstrated to inhibit platelet aggregation, relax smooth muscle cells, and control cardiocyte contractility. There are two subtypes of the type I cGK, cGKIα and cGKIβ. The former is more sensitive to cGMP than the latter. In humans, cGKIβ cDNA was isolated, but the full structure and tissue-specific gene expression of cGKIα have not been determined. The significance of cGK in human cardiovascular diseases has not been investigated at the molecular level. In the present study, we isolated the full-length human cGKIα cDNA (-36 to +2177: the translation start site: +1) encoding the 671-amino acid protein. Nucleotides +267 to +2177 of the isolated cDNA were identical to the corresponding nucleotides of human cGKIβ cDNA. Southern blot analysis suggested that human cGKIα and cGKIβ are generated by alternative splicing of a single gene assigned to chromosome 10. By Northern blot analysis, we detected abundant human cGKIα mRNA (7.0 kb) in the aorta, heart, kidneys, and adrenals. In contrast, human cGKIβ mRNA (7.0 kb) was detected abundantly only in the uterus. In cultured vascular smooth muscle cells, the type I cGK mRNA concentration was reduced to 10% of the basal level by 4 x 10 -10 mol/L platelet-derived growth factor. Angiotensin II (10 -8 mol/L), transforming growth factor-β (4 x 10 -11 mol/L), and tumor necrosis factor-α (6 x 10 -6 mol/L) also exhibited an inhibitory effect on type I cGK gene expression. These findings suggest a pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis.

Original languageEnglish
Pages (from-to)552-557
Number of pages6
JournalHypertension
Volume27
Issue number3 II
Publication statusPublished - 1996 Mar 1
Externally publishedYes

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Keywords

  • angiotensin II
  • cloning, molecular
  • growth substances
  • muscle, smooth, vascular
  • platelet-derived growth factor
  • protein kinases

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Tamura, N., Itoh, H., Ogawa, Y., Nakagawa, O., Harada, M., Chun, T. H., Suga, S. I., Yoshimasa, T., & Nakao, K. (1996). cDNA cloning and gene expression of human type Iα cGMP-dependent protein kinase. Hypertension, 27(3 II), 552-557.