Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stepan, V; Sugano, K; Yamada, T; Park, J; Dickinson, CJ.
Gastrin biosynthesis in canine G cells.
Am J Physiol Gastrointest Liver Physiol. 2002; 282(5):G766-G775
Doi: 10.1152/ajpgi.00167.2001
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- Führende Autor*innen der Med Uni Graz
- Stepan Vinzenz
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- Abstract:
- Gastrin requires extensive posttranslational processing for full biological activity. It is presumed that progastrin is cleaved at pairs of basic amino acids by a prohormone convertase to form a glycine-extended intermediate (G-Gly) that serves as a substrate for peptidyl-glycine alpha-amidating monooxygenase (PAM), resulting in COOH-terminally amidated gastrin. To confirm the nature of progastrin processing in a primary cell line, we performed [(35)S]methionine-labeled pulse-chase biosynthetic experiments in canine antral G cells. Radiolabeled progastrin reached a peak earlier than observed for G-Gly or amidated gastrin. G-Gly radioactivity accumulated in G cells and preceded the appearance of radioactivity in amidated gastrin. The conversion of G-Gly to amidated gastrin was enhanced by the PAM cofactor ascorbic acid. To determine whether one member of the prohormone convertase family (PC2) was responsible for progastrin cleavage, G cells were incubated with PC2 antisense oligonucleotide probes. Cells treated with antisense probes had reduced PC2 expression, an accumulation of radiolabeled progastrin, and a delay in the formation of amidated gastrin. Progastrin in antral G cells is cleaved via PC2 to form G-Gly that is converted to amidated gastrin via the actions of PAM.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cells, Cultured -
- Dogs -
- Gastrins - biosynthesis Gastrins - metabolism
- Gene Expression Regulation, Enzymologic -
- Glycine - metabolism
- Methionine - pharmacokinetics
- Mixed Function Oxygenases - metabolism
- Multienzyme Complexes - metabolism
- Oligonucleotides, Antisense - pharmacology
- Proprotein Convertase 2 -
- Pyloric Antrum - cytology Pyloric Antrum - enzymology
- Subtilisins - genetics Subtilisins - metabolism
- Sulfur Radioisotopes - diagnostic use
- Find related publications in this database (Keywords)
- COOH-terminally amidated gastrin
- prohormone convertase
- peptidyl-glycine alpha-amidating monooxygenase
- glycine