Abstract
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.
MeSH terms
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Animals
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Aprotinin / pharmacology
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Atrial Natriuretic Factor / biosynthesis
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Atrial Natriuretic Factor / genetics
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Atrial Natriuretic Factor / metabolism*
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Benzamidines / pharmacology
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COS Cells
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Catalysis
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Cell Line
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Cricetinae
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Gene Expression
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Humans
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Leupeptins / pharmacology
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Protein Precursors / biosynthesis
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Protein Processing, Post-Translational*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Serine Endopeptidases / biosynthesis
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Trypsin Inhibitors / pharmacology
Substances
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Benzamidines
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Leupeptins
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Membrane Proteins
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Protein Precursors
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Recombinant Fusion Proteins
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Serine Proteinase Inhibitors
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Trypsin Inhibitors
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Atrial Natriuretic Factor
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Aprotinin
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CORIN protein, human
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Serine Endopeptidases
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leupeptin
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benzamidine