Proteolytic processing of chromogranin A by the prohormone convertase PC2.

Abstract

The neuroendocrine secretory protein chromogranin A (CgA) is a precursor for various biologically active peptides. Several single and paired basic residues are present within its primary amino acid sequence comprising cleavage sites for prohormone convertases. In this study, SH-SY5Y human neuroblastoma cells were stably transfected with the prohormone convertase PC2 to analyse the proteolytic processing of endogenous chromogranin A and, in particular, the formation of the chromogranin-A-derived peptide GE-25. Our analyses revealed a significant change in the pattern of proteolytic conversion of chromogranin A in cells expressing PC2. Mock-transfected control cells contained mainly the intact chromogranin A molecule and hardly any shorter products were found. On the other hand, PC2-transfected cells showed extensive processing of chromogranin A, resulting in significantly lower amounts of the intact precursor and especially high levels of the free peptide GE-25.

• Authors: Alfred Doblinger, Alexandra Becker, Nabil G Seidah, Andrea Laslop
• Journal: Regulatory peptides (Regul Pept) Vol. 111 Issue 1-3 Pg. 111-6 (Mar 28 2003) ISSN: 0167-0115 [Print] Netherlands
• PMID: 12609757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Elsevier Science B.V.

Chemical References

• CHGA protein, human
• Chromogranin A
• Chromogranins
• Neoplasm Proteins
• Peptide Fragments
• Proprotein Convertase 2

Topics

• Blotting, Northern
• Chromogranin A
• Chromogranins (metabolism)
• Cloning, Molecular
• Humans
• Immunoblotting
• Neoplasm Proteins (genetics, metabolism)
• Neuroblastoma (metabolism)
• Peptide Fragments (metabolism)
• Proprotein Convertase 2 (genetics, metabolism)
• Protein Processing, Post-Translational
• Radioimmunoassay
• Transfection
• Tumor Cells, Cultured