Y. Okumura, M. Nishikawa, P. Cui, M. Shiota, Y. Nakamura, M. Adachi, K. Kitamura, K. Tomita, H. Kido
Cloning and Characterization of a Transmembrane-Type Serine Protease from Rat Kidney, a New Sodium Channel Activator
We have cloned the gene of a new transmembranetype
serine protease from rat kidney, which activates
sodium channels. The amino acid sequence deduced
from a full-length cDNA revealed that transmembrane
serine protease-1 (TMSP-1) is a member of the clan
SA/family S1 of serine proteases, comprising a 30
amino acid prepropeptide, a mature form sequence
of 274 amino acids starting with the Ile-Val-Gly-Gly-Gln motif, and a common catalytic triad of serine proteases.
The hydrophobic amino acid sequence in the
carboxyterminus of this enzyme suggests that it is a
glycosylphosphatidylinositol-anchored protein. As
revealed by quantitative reverse transcription-polymerase
chain reaction analysis, it is highly expressed
in kidney, small intestine, and stomach, and moderately
expressed in lung, thymus, spleen and skin. The
recombinant protease had an optimal pH at 9.0, selectively
cleaved synthetic peptide substrates of
trypsin, and was inhibited by aprotinin, leupeptin and
benzamidine. Immunohistochemical studies revealed
that this protease is predominantly expressed in cells
from collecting ducts of the renal medulla. We also
demonstrate that a C-terminally truncated variant of
TMSP-1 significantly activates the epithelial sodium
channel, and that its mRNA levels are upregulated by
aldosterone. These observations suggest that it is a
new member of the trypsin-type transmembrane proteases,
which regulate sodium balance by activating
the epithelial sodium channel.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 384, 11/2003
Pages: 1483 - 1495
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