Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme

Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8525-9. doi: 10.1073/pnas.150149097.

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

  • Animals
  • Aprotinin / pharmacology
  • Atrial Natriuretic Factor / biosynthesis
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism*
  • Benzamidines / pharmacology
  • COS Cells
  • Catalysis
  • Cell Line
  • Cricetinae
  • Gene Expression
  • Humans
  • Leupeptins / pharmacology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Trypsin Inhibitors / pharmacology

Substances

  • Benzamidines
  • Leupeptins
  • Membrane Proteins
  • Protein Precursors
  • Recombinant Fusion Proteins
  • Serine Proteinase Inhibitors
  • Trypsin Inhibitors
  • Atrial Natriuretic Factor
  • Aprotinin
  • CORIN protein, human
  • Serine Endopeptidases
  • leupeptin
  • benzamidine