Akt通过Dishevelled参与Wnt信号通路。

Akt participation in the Wnt signaling pathway through Dishevelled.

作者信息

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

机构信息

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.

出版信息

J Biol Chem. 2001 May 18;276(20):17479-83. doi: 10.1074/jbc.C000880200. Epub 2001 Mar 9.

DOI:10.1074/jbc.C000880200

PMID:11278246

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.

摘要

糖原合酶激酶3β（GSK3β）的失活以及由此导致的游离β-连环蛋白的稳定是Wnt靶基因激活过程中的关键步骤。虽然Akt在磷脂酰肌醇3-OH激酶信号通路中调节GSK3α/β，但其在Wnt信号传导中的作用尚不清楚。在此我们报告，Wnt或散乱蛋白（Dvl）的表达增加了Akt活性。在Dvl存在的情况下，活化的Akt与Axin-GSK3β复合物结合，使GSK3β磷酸化并增加游离β-连环蛋白水平。此外，在过表达Wnt的PC12细胞中，显性负性Akt降低了游离β-连环蛋白水平并解除了神经生长因子诱导的分化抑制。因此，Akt与Dvl协同作用，作为Wnt信号通路的重要调节因子。