No abstract

Axin, a negative regulator of the Wnt signaling pathway, forms a complex with glycogen synthase kinase-3␤ (GSK-3␤), ␤-catenin, adenomatous polyposis coli (APC) gene product, and Dvl, and it regulates GSK-3␤-dependent phosphorylation in the complex and the stability of ␤-catenin. Using yeast two-hybrid screening, we found that regulatory subunits of protein phosphatase 2A, PR61␤ and -␥, interact with Axin. PR61␤ or -␥ formed a complex with Axin in intact cells, and their interaction was direct. The binding site of PR61␤ on Axin was different from those of GSK-3␤, ␤-catenin, APC, and Dvl. Although PR61␤ did not affect the stability of ␤-catenin, it inhibited Dvl-and ␤-catenin-dependent T cell factor activation in mammalian cells. Moreover, it suppressed ␤-catenin-induced axis formation and expression of siamois, a Wnt target gene, in Xenopus embryos, suggesting that PR61␤ acts either at the level of ␤-catenin or downstream of it. Taken together with the previous observations that PR61 interacts with APC and functions upstream of ␤-catenin, these results demonstrate that PR61 regulates the Wnt signaling pathway at various steps.