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Akt participation in the Wnt signaling pathway through Dishevelled
Authors:Fukumoto S  Hsieh C M  Maemura K  Layne M D  Yet S F  Lee K H  Matsui T  Rosenzweig A  Taylor W G  Rubin J S  Perrella M A  Lee M E
Institution:Cardiovascular and Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and the Cardiovascular Research Center Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:Inactivation of glycogen synthase kinase 3beta (GSK3beta) and the resulting stabilization of free beta-catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3alpha/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 Axin-GSK3beta complex in the presence of Dvl, phosphorylated GSK3beta 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.
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