| First Author | He H | Year | 2008 |
| Journal | Biochim Biophys Acta | Volume | 1783 |
| Issue | 10 | Pages | 1943-54 |
| PubMed ID | 18515095 | Mgi Jnum | J:140789 |
| Mgi Id | MGI:3814628 | Doi | 10.1016/j.bbamcr.2008.04.016 |
| Citation | He H, et al. (2008) PAK1 interacts with beta-catenin and is required for the regulation of the beta-catenin signalling pathway by gastrins. Biochim Biophys Acta 1783(10):1943-54 |
| abstractText | Beta-catenin regulates cell-cell adhesion by binding to E-cadherin at the cell membrane and, when translocated into the nucleus, mediates signalling by activation of transcription factors such as TCF4. Mutations of the components of the Wnt/beta-catenin pathway are found in many gastrointestinal cancers. Gastrins, including amidated (Gamide) and glycine-extended (Ggly) gastrin(17), stimulate the proliferation of gastrointestinal cancer cells. Gastrins also regulate beta-catenin signalling through multiple pathways which seem to converge on p21-activated kinase 1 (PAK1). In this study, we have investigated the role of PAK1 in the regulation of beta-catenin signalling by gastrins. Here we report for the first time that PAK1 associated with beta-catenin. Both Gamide and Ggly stimulated the phosphorylation and activation of beta-catenin in a PAK1-dependent manner. A kinase-inactive mutant PAK1(K299A) blocked the gastrin-stimulated dissociation of beta-catenin from E-cadherin, translocation of beta-catenin from the cell membrane to the nucleus, and association of beta-catenin with the transcription factor TCF4. The PAK1(K299A) mutant also inhibited the stimulation of the expression of c-myc and cyclin D1, and of cell proliferation and migration, by gastrins. The results indicate that gastrins regulate beta-catenin signalling through a PAK1-dependent pathway. PAK1 seems to be the point of convergence of multiple signalling pathways activated by gastrins. |
