Wnt3A Induces GSK-3β Phosphorylation and β-Catenin Accumulation Through RhoA/ROCK

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• 作者：Jae-Gyu Kim ; Myoung-Ju Kim ; Won-Ji Choi ; Mi-Young Moon ; Hee-Jun Kim ; Jae-Yong Lee ; Jaebong Kim ; Sung-Chan Kim ; Seung Goo Kang ; Goo-Young Seo ; Pyeung-Hyeun Kim and Jae-Bong Park
• 刊名：Journal of Cellular Physiology
• 出版年：2017
• 出版时间：May 2017
• 年：2017
• 卷：232
• 期：5
• 页码：1104-1113
• 全文大小：2755K
• ISSN：1097-4652

文摘

In canonical pathway, Wnt3A has been known to stabilize β-catenin through the dissociation between β-catenin and glycogen synthase kinase-3β (GSK-3β) that suppresses the phosphorylation and degradation of β-catenin. In non-canonical signaling pathway, Wnt was known to activate Rho GTPases and to induce cell migration. The cross-talk between canonical and non-canonical pathways by Wnt signaling; however, has not been fully elucidated. Here, we revealed that Wnt3A induces not only the phosphorylation of GSK-3β and accumulation of β-catenin but also RhoA activation in RAW264.7 and HEK293 cells. Notably, sh-RhoA and Tat-C3 abolished both the phosphorylation of GSK-3β and accumulation of β-catenin. Y27632, an inhibitor of Rho-associated coiled coil kinase (ROCK) and si-ROCK inhibited both GSK-3β phosphorylation and β-catenin accumulation. Furthermore, active domain of ROCK directly phosphorylated the purified recombinant GSK-3β in vitro. In addition, Wnt3A-induced cell proliferation and migration, which were inhibited by Tat-C3 and Y27632. Taken together, we propose the cross-talk between canonical and non-canonical signaling pathways of Wnt3A, which induces GSK-3β phosphorylation and β-catenin accumulation through RhoA and ROCK activation. J. Cell. Physiol. 232: 1104–1113, 2017.