Processing of proendothelin‐1 by human furin convertase

FEBS Letters

Sawamura, Tatsuya¹  Claing, Audrey²  Leduc, Richard²  Masaki, Tomoh¹  Kido, Tsuneo¹  D'Orléans-Juste, Pedro²  Denault, Jean-Bernard² 

[1] Department of Pharmacology, Medical School, Kyoto University, Kyoto 606, Japan;Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

关键词: Endothelin-1;    Precursor processing;    Furin;    Convertase;    Proteolytic inhibition;    Endothelial cell;   

DOI  :  10.1016/0014-5793(95)00249-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown