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Am J Physiol Gastrointest Liver Physiol 260: G783-G788, 1991;
0193-1857/91 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 260, Issue 5 783-G788, Copyright © 1991 by American Physiological Society

ARTICLES

Expression and processing of human preprogastrin in murine medullary thyroid carcinoma cells

D. F. Daugherty, C. J. Dickinson, T. Takeuchi, D. Bachwich and T. Yamada
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.

Gastrin, the primary hormonal mediator of postprandial gastric acid secretion, is produced from its precursor progastrin by a series of posttranslational processing reactions including dibasic residue cleavage and carboxyl-terminal alpha-amidation. Progastrin contains three dibasic cleavage signals, Arg57Arg58, Lys74Lys75, and Arg94Arg95, that appear to be cleaved differently in different tissues. Differential processing is a potential means by which the production of biologically active peptides may be regulated in a tissue-specific manner. To study these reactions further, we used the pZipNeo SV(X) retroviral vector to express human gastrin cDNA in a heterologous cell line (MTC 6-23) known to be capable of processing other peptide precursors. The psi 2 packaging cell line transfected with the gastrin cDNA-retroviral construct (pSVXgas) produced progastrin, but no substantial amounts of processed amidated gastrin were detected. amounts of processed amidated gastrin were detected. In contrast, MTC 6-23 cells infected with the viral stock obtained from the supernatant of pSVXgas-transfected psi 2 cells produced carboxyl-terminally amidated gastrin in all of its standard molecular forms, including sulfated and nonsulfated forms of tetratriacontagastrin (G-34), heptadecagastrin (G-17), and tetradecagastrin (G-14). These studies indicate that heterologous endocrine cell lines infected with a retroviral-peptide cDNA construct can serve as useful models for peptide hormone posttranslational processing.


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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
V. Stepan, K. Sugano, T. Yamada, J. Park, and C. J. Dickinson
Gastrin biosynthesis in canine G cells
Am J Physiol Gastrointest Liver Physiol, May 1, 2002; 282(5): G766 - G775.
[Abstract] [Full Text] [PDF]


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