TY - JOUR
T1 - ECE-1
T2 - A membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1
AU - Xu, Dong
AU - Emoto, Noriaki
AU - Giaid, Adel
AU - Slaughter, Clive
AU - Kaw, Semiko
AU - deWit, Damiane
AU - Yanagisawa, Masashi
N1 - Funding Information:
We thank Mike Brown and Joe Goldstein for reading manuscripts, Roger Corder for discussion, Sumio Kiyoto for samples of FR901533 and FR139317, and Nobuhiro Suzuki for EIA antibodies. This work is supported in part by research grants from the Perot Family Foundation (M.Y.), the Heart and Stroke Foundation of Canada (A.G.), and the Medical Research Council of Canada (A.G.).
PY - 1994/8/12
Y1 - 1994/8/12
N2 - Endothelin-1 (ET-1), a 21-residue vasoactive peptide, is produced in vascular endothelial cells from the 38-residue inactive intermediate big endothelin-1 via a specific cleavage at Trp-21-Val-22. The protease that catalyzes the conversion, endothelin-converting enzyme (ECE), constitutes a potential regulatory site for the production of the active peptide. We report the identification of ECE-1, a novel membrane-bound neutral metalloprotease that is expressed abundantly in endothelial cells in vivo and is structurally related to neutral endopeptidase 24.11 and Kell blood group protein. When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1. In transfected cells, ECE-1 processes endogenously synthesized big ET-1 as well as exogenously supplied big ET-1, which interacts with ECE-1 on the cell surface. ECE-1 may provide a target for pharmacological intervention to alter ET-1 production.
AB - Endothelin-1 (ET-1), a 21-residue vasoactive peptide, is produced in vascular endothelial cells from the 38-residue inactive intermediate big endothelin-1 via a specific cleavage at Trp-21-Val-22. The protease that catalyzes the conversion, endothelin-converting enzyme (ECE), constitutes a potential regulatory site for the production of the active peptide. We report the identification of ECE-1, a novel membrane-bound neutral metalloprotease that is expressed abundantly in endothelial cells in vivo and is structurally related to neutral endopeptidase 24.11 and Kell blood group protein. When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1. In transfected cells, ECE-1 processes endogenously synthesized big ET-1 as well as exogenously supplied big ET-1, which interacts with ECE-1 on the cell surface. ECE-1 may provide a target for pharmacological intervention to alter ET-1 production.
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U2 - 10.1016/0092-8674(94)90425-1
DO - 10.1016/0092-8674(94)90425-1
M3 - Article
C2 - 8062389
AN - SCOPUS:0027992642
SN - 0092-8674
VL - 78
SP - 473
EP - 485
JO - Cell
JF - Cell
IS - 3
ER -