Akt participation in the Wnt signaling pathway through dishevelled

被引：307
作者：
Fukumoto, S
Hsieh, CM
Maemura, K
Layne, RD
Yet, SF
Lee, KH
Matsui, T
Rosenzweig, A
Taylor, WG
Rubin, JS
Perrella, MA
Lee, ME
机构：
[1] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA
[5] NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2001年 / 276卷 / 20期
关键词：
D O I：
10.1074/jbc.C000880200
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：17479 / 17483
页数：5
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