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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||URI:||http://ahro.austin.org.au/austinjspui/handle/1/10629||DOI:||10.1016/j.biocel.2008.05.002||URL:||https://pubmed.ncbi.nlm.nih.gov/18565785||Type:||Journal Article||Subjects:||Animals
rho GTP-Binding Proteins.metabolism
|Appears in Collections:||Journal articles|
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