Akt Participation in the Wnt Signaling Pathway through Dishevelled
2001
Abstract Inactivation of glycogen synthase kinase 3β (GSK3β) and the resulting stabilization of free β-catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3α/β 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 Axin-GSK3β complex in the presence of Dvl, phosphorylated GSK3β and increased free β-catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free β-catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway.
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