title: Processing of proendothelin-1 by human furin convertase.
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-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.
authors.affiliation: Department of Pharmacology, Medical School, Kyoto University, Japan.
authors.forename: J B
authors.initials: JB
authors.lastname: Denault
authors.forename: A
authors.initials: A
authors.lastname: Claing
authors.forename: P
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: T
authors.initials: T
authors.lastname: Sawamura
authors.forename: T
authors.initials: T
authors.lastname: Kido
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: R
authors.initials: R
authors.lastname: Leduc
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D045683:Furin; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013381:Subtilisins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D014649:Vas Deferens / Q000502:physiology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D011994:Recombinant Proteins; C093240:proendothelin 1; D013381:Subtilisins; D045683:Furin