Akt participation in the Wnt signaling pathway through dishevelled
Akt participation in the Wnt signaling pathway through dishevelled
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DOI：
10.1074/jbc.c000880200
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发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Lee, ME
中科院分区：
文献类型：
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作者：
Fukumoto, S;Hsieh, CM;Lee, ME
糖原合成酶激酶3 β（GSKS β）的失活和游离β-连环蛋白的稳定是Wnt靶基因活化的关键步骤。虽然Akt在磷脂酰肌醇3-OH激酶信号通路中调节GSK 3 α/β，但其在Wnt信号通路中的作用尚不清楚。在这里，我们报告说，表达Wnt或Dishevelled（Dvl）增加Akt活性。活化的Akt在Dvl、磷酸化的GSK 3 β和增加的游离β-连环蛋白水平的存在下与Axrin-GSK 3 β复合物结合。此外，在Wnt过表达的PC 12细胞中，显性阴性Akt减少游离β-连环蛋白和去抑制神经生长因子诱导的分化。因此，Akt作为Wnt信号通路的重要调节剂与Dvl联合作用。
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.