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Volume 362, Issue 3 p. 276-280
Research letter
Free Access

Processing of proendothelin-1 by human furin convertase

Jean-Bernard Denault

Jean-Bernard Denault

Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

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Audrey Claing

Audrey Claing

Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

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Pedro D'Orléans-Juste

Pedro D'Orléans-Juste

Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

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Tatsuya Sawamura

Tatsuya Sawamura

Department of Pharmacology, Medical School, Kyoto University, Kyoto 606, Japan

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Tsuneo Kido

Tsuneo Kido

Department of Pharmacology, Medical School, Kyoto University, Kyoto 606, Japan

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Tomoh Masaki

Tomoh Masaki

Department of Pharmacology, Medical School, Kyoto University, Kyoto 606, Japan

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Richard Leduc

Richard Leduc

Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

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First published: April 10, 1995
Citations: 74
Corresponding author.

Abstract

Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-ValLys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.