Proteolytic processing of chromogranin A by the prohormone convertase PC2.
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.
Doblinger
Alfred
A
Department of Pharmacology, University of Innsbruck, Peter-Mayr-Strasse 1a, A-6020, Innsbruck, Austria.
Becker
Alexandra
A
Seidah
Nabil G
NG
Laslop
Andrea
A
D015152:Blotting, Northern; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011863:Radioimmunoassay; D014162:Transfection; D014407:Tumor Cells, Cultured
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D045706:Proprotein Convertase 2