ECE-1 - A MEMBRANE-BOUND METALLOPROTEASE THAT CATALYZES THE PROTEOLYTIC ACTIVATION OF BIG ENDOTHELIN-1
ECE-1 - A MEMBRANE-BOUND METALLOPROTEASE THAT CATALYZES THE PROTEOLYTIC ACTIVATION OF BIG ENDOTHELIN-1
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DOI：
10.1016/0092-8674(94)90425-1
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发表时间：
1994-08-12
期刊：
影响因子：
64.5
通讯作者：
YANAGISAWA, M
中科院分区：
文献类型：
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作者：
XU, D;EMOTO, N;YANAGISAWA, M
内皮素-1 （ET-1）是一种具有21个残基的血管活性肽，由38个残基无活性的中间大内皮素-1通过在Trp-21-Val-22上的特异性裂解产生。催化这种转化的蛋白酶，内皮素转换酶（ECE），构成了活性肽生产的潜在调控位点。我们报道了一种新的膜结合中性金属蛋白酶ECE-1的鉴定，该酶在体内内皮细胞中大量表达，并且在结构上与中性内肽酶24.11和Kell血型蛋白相关。当转染到通常只分泌大ET-1的培养细胞中时，ECE-1 cDNA赋予了分泌成熟ET-1的能力。在转染的细胞中，ECE-1处理内源性合成的大ET-1和外源性提供的大ET-1，后者在细胞表面与ECE-1相互作用。ECE-1可能为改变ET-1产生的药物干预提供靶点。
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.