Prohormone convertase-1 is essential for conversion of chromogranin A to pancreastatin

• Published in: Regulatory peptides Vol. 83; no. 2; pp. 123 - 127
• Main Authors: Udupi, Vidyavathi, Lee, Heung-Man, Kurosky, Alexander, Greeley, George H
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.09.1999; Amsterdam Elsevier
• Subjects: Antisense; Apud cells. Peptide and protein hormones. Growth factors; Aspartic Acid Endopeptidases - genetics; Aspartic Acid Endopeptidases - physiology; Biological and medical sciences; Carcinoid Tumor - enzymology; Carcinoid Tumor - metabolism; Chromatography, High Pressure Liquid; Chromogranin A; Chromogranins - metabolism; Endoprotease; Fundamental and applied biological sciences. Psychology; Humans; Pancreatic Hormones - biosynthesis; Pancreatic Hormones - metabolism; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - metabolism; Peptide; Processing; Proprotein Convertases; RNA, Messenger - metabolism; Transfection; Tumor Cells, Cultured; Vertebrates: endocrinology; Endoprotease; Antisense; Peptide; Processing; Peptidases; Proprotein convertase I; Chromogranin; Serine endopeptidases; Metabolic precursor; Enzyme; Pancreastatin; Hydrolases; Biosynthesis
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/S0167-0115(99)00061-0

The purpose of this study was to test the hypothesis that the endoprotease, prohormone convertase-1 (PC-1), is involved in the processing of the precursor protein chromogranin A (CGA) to a smaller peptide called pancreastatin (PST). A human pancreatic carcinoid cell line (BON) that expresses PC-1, CGA and PST was stably transfected with antisense PC-1 mRNA. BON cells expressing antisense PC-1 mRNA showed nearly complete abolishment of PC-1 protein (∼95% reduction) and an 80% reduction in cell content of PST immunoreactivity (PST-IR) as assessed by high-performance liquid chromatography in combination with measurement of PST-IR. These findings indicate that PC-1 is essential for processing CGA to PST.