ECE-1: A membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1

Dong Xu, Noriaki Emoto, Adel Giaid, Clive Slaughter, Semiko Kaw, Damiane deWit, Masashi Yanagisawa

Research output: Contribution to journalArticle

836 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)473-485
Number of pages13
JournalCell
Volume78
Issue number3
DOIs
StatePublished - Aug 12 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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