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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Amino Acid Sequence
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Animals
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Cattle
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Endothelin-1
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Endothelins / biosynthesis
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Endothelins / genetics
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Endothelins / isolation & purification
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Endothelins / metabolism*
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Endothelium, Vascular / metabolism
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Furin
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Humans
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Male
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Molecular Sequence Data
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Molecular Weight
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / physiology
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Protein Precursors / biosynthesis
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Protein Precursors / genetics
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Protein Precursors / isolation & purification
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Protein Precursors / metabolism*
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Rabbits
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Rats
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Rats, Wistar
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / isolation & purification
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Subtilisins / antagonists & inhibitors
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Subtilisins / isolation & purification
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Subtilisins / metabolism*
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Vas Deferens / physiology
Substances
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Amino Acid Chloromethyl Ketones
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Endothelin-1
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Endothelins
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Protein Precursors
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Recombinant Proteins
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proendothelin 1
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Subtilisins
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Furin