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Title: Rho GTPases and p21-activated kinase in the regulation of proliferation and apoptosis by gastrins.
Austin Authors: He, Hong ;Baldwin, Graham S
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia
Issue Date: 15-May-2008
Publication information: The International Journal of Biochemistry & Cell Biology 2008; 40(10): 2018-22
Abstract: Gastrins, including amidated gastrin (Gamide) and glycine-extended gastrin (Ggly), accelerate the growth of gastrointestinal cancer cells by stimulation of proliferation and inhibition of apoptosis. Gamide and Ggly activate different G proteins of the Rho family of small GTPases. For example, Gamide signals Rac/Cdc42 to activate p21-activated kinase 1 while Ggly signals Rho to activate Rho-activated kinase. p21-activated kinase 1 and Rho-activated kinase induce changes in phosphorylation or expression, respectively, of proteins of the Bcl-2 family, which then affect the caspase cascade with consequent inhibition of apoptosis. In addition, interaction of p21-activated kinase 1 with beta-catenin results in phosphorylation of beta-catenin, which enhances its translocation in to the nucleus, activation of TCF4-dependent transcription, and proliferation and migration. The central role of the beta-catenin pathway in carcinogenesis suggests that specific inhibitors of p21-activated kinase 1 may in the future provide novel therapies for gastrointestinal malignancies.
Gov't Doc #: 18565785
DOI: 10.1016/j.biocel.2008.05.002
Journal: The international journal of biochemistry & cell biology
Type: Journal Article
Subjects: Animals
Cell Proliferation
p21-Activated Kinases.metabolism
rho GTP-Binding Proteins.metabolism
Appears in Collections:Journal articles

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