Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stepan, VM; Krametter, DF; Matsushima, M; Todisco, A; Delvalle, J; Dickinson, CJ.
Glycine-extended gastrin regulates HEK cell growth.
Am J Physiol. 1999; 277(2 Pt 2):R572-R581
Doi: 10.1152/ajpregu.1999.277.2.R572
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- Führende Autor*innen der Med Uni Graz
- Stepan Vinzenz
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- Abstract:
- Posttranslational processing of progastrin to a carboxy terminally amidated form (G-NH(2)) is essential for its effect on gastric acid secretion and other biological effects mediated by gastrin/CCK-B receptors. The immediate biosynthetic precursor of G-NH(2), glycine-extended gastrin (G-Gly), does not stimulate gastric acid secretion at physiological concentrations but is found in high concentrations during development. G-NH(2) and G-Gly have potent growth stimulatory effects on gastrointestinal tissues, and G-NH(2) can stimulate proliferation of human kidney cells. Thus we sought to explore the actions of G-NH(2) and G-Gly on the human embryonic kidney cell line HEK 293. HEK 293 cells showed specific binding sites for (125)I-labeled Leu(15)-G17-NH(2) and (125)I-Leu(15)-G(2-17)-Gly. Both G-NH(2) and G-Gly induced a dose-dependent increase in [(3)H]thymidine incorporation, and both peptides together significantly increased [(3)H]thymidine incorporation above the level of either peptide alone. G-NH(2) and G-Gly were detected by radioimmunoassay in serum-free conditioned media. Antibodies directed against G-NH(2) and G-Gly lead to a significant reduction in [(3)H]thymidine incorporation. G-NH(2) but not G-Gly increased intracellular Ca(2+) concentration. We conclude that G-NH(2) and G-Gly act cooperatively via distinct receptors to stimulate the growth of a nongastrointestinal cell line (HEK 293) in an autocrine fashion.
- Find related publications in this database (using NLM MeSH Indexing)
- Binding Sites -
- Calcium - metabolism
- Cell Division - drug effects
- Cell Line -
- Embryo, Mammalian - cytology
- Gastrins - genetics Gastrins - metabolism Gastrins - pharmacology
- Gene Expression -
- Humans -
- Immunoblotting -
- Intracellular Membranes - metabolism
- Kidney - embryology
- Osmolar Concentration -
- Receptor, Cholecystokinin B -
- Receptors, Cholecystokinin - metabolism
- Receptors, Glycine - metabolism
- Find related publications in this database (Keywords)
- cholecystokinin-B receptor
- human embryonic kidney cell
- cellular proliferation