Akt participation in the Wnt signaling pathway through dishevelled

Inactivation of glycogen synthase kinase 3 beta (GSKS beta) and the resulting stabilization of free beta -catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3 alpha/beta in the phosphatidylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axrin-GSK3 beta complex in the presence of Dvl, phosphorylated GSK3 beta and increased free beta -catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free beta -catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway.