Processing of proendothelin-1 by members of the subtilisin-like pro-protein convertase family.
Endothelial cells (ECs) secrete numerous bioactive peptides that are initially synthesized as inactive precursor proteins. One of these, proendothelin-1 (proET-1), undergoes proteolysis at specific pairs of basic amino acids. Here, we wished to examine the role of mammalian convertases in this event. Northern blot analysis shows that only furin and PC7 are expressed in ECs. In vitro cleavage of proET-1 by furin or PC7 demonstrated that both enzymes efficiently and specifically process proET-1. These data reveal that furin and PC7 have similar specificities towards proET-1 and suggest that both enzymes may participate in the maturation of proET-1 in ECs.
Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, QC, Canada.
Véronique
V
Blais
Martin
M
Fugère
Jean-Bernard
JB
Denault
Klaus
K
Klarskov
Robert
R
Day
Richard
R
Leduc
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D013381:Subtilisins / Q000378:metabolism*
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D011994:Recombinant Proteins; C093240:proendothelin 1; D043484:Proprotein Convertases; D013381:Subtilisins