Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme.
Atrial natriuretic peptide (ANP) is a cardiac hormone essential for the regulation of blood pressure. In cardiac myocytes, ANP is synthesized as a precursor, pro-ANP, that is converted to biologically active ANP by an unknown membrane-associated protease. Recently, we cloned a transmembrane serine protease, corin, that is highly expressed in the heart. In this study, we examine effects of corin on pro-ANP processing. Our results show that recombinant human corin converts pro-ANP to ANP and that the cleavage in pro-ANP by corin is highly sequence specific. Our findings suggest that corin is the long-sought pro-ANP-converting enzyme and that the corin-mediated pro-ANP activation may play a role in regulating blood pressure.
Yan
W
W
Department of Cardiovascular Research, Berlex Biosciences, 15049 San Pablo Avenue, Richmond, CA 94804, USA.
Wu
F
F
Morser
J
J
Wu
Q
Q
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001550:Benzamidines / Q000494:pharmacology; D019556:COS Cells; D002384:Catalysis; D002460:Cell Line; D006224:Cricetinae; D015870:Gene Expression; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000494:pharmacology
D001550:Benzamidines; D007976:Leupeptins; D008565:Membrane Proteins; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D009320:Atrial Natriuretic Factor; D007611:Aprotinin; C119812:CORIN protein, human; D012697:Serine Endopeptidases; C032854:leupeptin; C032157:benzamidine