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

• Published in: Journal of cellular physiology 2017-05, Vol.232 (5), p.1104-1113
• Main Authors: Kim, Jae‐Gyu, Kim, Myoung‐Ju, Choi, Won‐Ji, Moon, Mi‐Young, Kim, Hee‐Jun, Lee, Jae‐Yong, Kim, Jaebong, Kim, Sung‐Chan, Kang, Seung Goo, Seo, Goo‐Young, Kim, Pyeung‐Hyeun, Park, Jae‐Bong
• Format: Article
• Language: English
• Subjects: Amides - pharmacology; Animals; beta Catenin - metabolism; Cell Movement - drug effects; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Proliferation - drug effects; Chemokines - metabolism; Glycogen Synthase Kinase 3 beta - metabolism; HEK293 Cells; Humans; Mice; Phosphorylation - drug effects; Protein Transport - drug effects; Pyridines - pharmacology; RAW 264.7 Cells; Recombinant Fusion Proteins - pharmacology; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - antagonists & inhibitors; rhoA GTP-Binding Protein - metabolism; Wnt3A Protein - pharmacology
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25572

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. © 2016 Wiley Periodicals, Inc. Wnt3A activates RhoA and ROCK, which induces GSK‐3beta phosphorylation and beta‐catenin accumulation. RhoA and ROCK are involved in the regulation of cell proliferation and migration upon Wnt3A.