Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10449
Title: Involvement of G proteins of the Rho family in the regulation of Bcl-2-like protein expression and caspase 3 activation by Gastrins.
Authors: He, Hong;Yim, Mildred;Liu, Kevin H;Cody, Stephen C;Shulkes, Arthur;Baldwin, Graham S
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria 3084, Australia. hong.he@unimelb.edu.au
Issue Date: 11-Sep-2007
Citation: Cellular Signalling 2007; 20(1): 83-93
Abstract: Gastrins, including amidated gastrin (Gamide) and glycine-extended gastrin (Ggly), are known to accelerate the growth of gastric and colorectal cancer cells by stimulation of proliferation and inhibition of apoptosis. Gamide controls apoptosis by regulation of proteins of the Bcl-2 family and by regulation of the activation of caspases. However the interactions between Ggly and proteins of the Bcl-2 family and caspases are not known. Since in other systems G proteins of the Rho family inhibit apoptosis via interaction with proteins of the Bcl-2 family, leading to changes in caspase activities, we have compared the role of Rho family G proteins in regulation of Bcl-2-like (Bad/Bax/Bcl-xl) protein expression and caspase 3 activation by Ggly and Gamide. The effects of the specific inhibitors C3 (for Rho) and Y-27632 (for ROCK), and of dominant negative mutants of Rac, Cdc42 and PAK, were investigated in the gastric epithelial cell line IMGE-5. Apoptosis was induced by serum starvation and confirmed by annexin V staining and caspase 3 activation. Ggly inhibits caspase 3 activation via a Bcl-2-like protein-mediated pathway which requires activation of both Rho/ROCK and Rac/Cdc42/PAK. Gamide inhibits caspase 3 activation via redundant Bcl-2-like protein-mediated pathways which involve alternative activation of Rac/Cdc42/PAK and Rho/ROCK. Gamide and Ggly differentially activate members of Rho family G proteins which in turn regulate different proteins of the Bcl-2 family leading to changes in caspase 3 activity. The findings offer potential targets for blocking the growth-stimulating effects of these gastrins.
Internal ID Number: 17936584
URI: http://ahro.austin.org.au/austinjspui/handle/1/10449
DOI: 10.1016/j.cellsig.2007.08.018
URL: http://www.ncbi.nlm.nih.gov/pubmed/17936584
Type: Journal Article
Subjects: Amides.pharmacology
Animals
Apoptosis.drug effects
Caspase 3.metabolism
Cell Line
Enzyme Inhibitors.pharmacology
Epithelial Cells.metabolism
Gastric Mucosa.cytology.metabolism
Gastrins.physiology
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-akt.metabolism
Proto-Oncogene Proteins c-bcl-2.metabolism
Pyridines.pharmacology
Signal Transduction.physiology
bcl-2-Associated X Protein.metabolism
bcl-X Protein.metabolism
cdc42 GTP-Binding Protein.metabolism
p21-Activated Kinases.metabolism
rho GTP-Binding Proteins.metabolism
rho-Associated Kinases.metabolism
Appears in Collections:Journal articles

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