(Hypertension. 1996;27:552-557.)
© 1996 American Heart Association, Inc.
Articles |
cGMP-Dependent Protein Kinase
From the Department of Medicine and Clinical Science, Kyoto (Japan) University Graduate School of Medicine.
Correspondence to Hiroshi Itoh, MD, PhD, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan. E-mail hiito@kuhp.kyoto-u.ac.jp.
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, cGKI
and cGKIß. The
former is more sensitive to cGMP than the latter. In humans, cGKIß
cDNA was isolated, but the full structure and tissue-specific gene
expression of cGKI
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 cGKI
cDNA (-36 to +2177;
the translation start site: +1) encoding the 671amino acid
protein.
Nucleotides +267 to +2177 of the isolated cDNA were
identical to the corresponding nucleotides of human cGKIß
cDNA. Southern blot analysis suggested that human cGKI
and
cGKIß are generated by alternative splicing of a single gene assigned
to chromosome 10. By Northern blot analysis, we detected
abundant human cGKI
mRNA (7.0 kb) in the aorta, heart, kidneys, and
adrenals. In contrast, human cGKIß 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 4x10-10 mol/L
platelet-derived growth factor. Angiotensin II
(10-8 mol/L), transforming growth
factor-ß (4x10-11 mol/L), and tumor
necrosis factor-
(6x10-6 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.
Key Words: protein kinases cloning, molecular muscle, smooth, vascular platelet-derived growth factor angiotensin II growth substances
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