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Processing of proendothelin‐1 by human furin convertase
Author(s) -
Denault Jean-Bernard,
Claing Audrey,
D'Orléans-Juste Pedro,
Sawamura Tatsuya,
Kido Tsuneo,
Masaki Tomoh,
Leduc Richard
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00249-9
Subject(s) - furin , proteolysis , prohormone convertase , cleavage (geology) , biochemistry , peptide , proprotein convertases , proprotein convertase , chemistry , endothelin 1 , amino acid , in vitro , biological activity , biology , enzyme , prohormone , hormone , lipoprotein , paleontology , ldl receptor , receptor , cholesterol , fracture (geology)
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.