Fig. 6.

PAK1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling molecules. Deletion of the gastrin gene resulted in a reduction in colorectal proliferation associated with decreased activation of PAK1, ERK, AKT, and β-catenin. Deletion of the PAK1 gene resulted in reduced colorectal proliferation associated with decreased activities of ERK, AKT, and β-catenin. PAK1 also negatively regulated gastrin production, since PAK1 KO mice had increased gastrin mRNA in the gastric mucosa and were hypergastrinemic. Together these results suggested that gastrins activate PAK1, which in turn enhances the activities of ERK, AKT, and β-catenin, and that the activation of these multiple signaling molecules contributes to proliferation in the colorectal mucosa.