Presence of furin mRNA in cultured bovine endothelial cells and possible involvement of furin in the processing of the endothelin precursor.
Recently it was documented that furin, a calcium-dependent serine endoprotease, cleaves many protein precursors at pairs of basic amino acids, thus liberating the biologically active peptides. The endothelin precursors follow a biosynthetic pathway similar to these proteins, where the precursor is initially processed to the intermediate, big endothelin (big ET) before its conversion to the endothelin (ET) peptide. Analysis of the amino acid sequence of the endothelin pro-proteins shows that they are susceptible to processing by endoproteases that cleave at pairs of basic amino acids. For example, human endothelin-1 (ET-1) precursor possesses a typical furin cleavage site motif (Arg-X-Lys/Arg-Arg) at the following residues: Arg32-Ser33-Lys34-Arg35 and Arg72-Ser73-Lys74-Arg75. We have isolated mRNA from cultured bovine endothelial cells and, using a human furin cRNA probe, shown that a furin mRNA of 4.5 kb is present in these cells. We propose that furin, a novel endoprotease belonging to the mammalian subtilisin family of serine proteases, may be implicated in the processing of pro-endothelin precursors, liberating big ET.
Laporte
S
S
Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
Denault
J B
JB
D'Orléans-Juste
P
P
Leduc
R
R
D000199:Actins / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D045683:Furin; D000882:Haplorhini; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000096:biosynthesis* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000276:immunology; D013381:Subtilisins / Q000096:biosynthesis*
D000199:Actins; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D013381:Subtilisins; D045683:Furin