Akt participation in the Wnt signaling pathway through dishevelled

Inactivation of glycogen synthase kinase 3 beta (GSKS beta) and the resulti ng stabilization of free beta -catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3 alpha/beta in the phosphatid ylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unk nown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axrin-GSK3 beta complex in the pre sence of Dvl, phosphorylated GSK3 beta and increased free beta -catenin lev els. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt d ecreased free beta -catenin and derepressed nerve growth factor-induced dif ferentiation. Therefore, Akt acts in association with Dvl as an important r egulator of the Wnt signaling pathway.