title: Wnt3A Induces GSK-3β Phosphorylation and β-Catenin Accumulation Through RhoA/ROCK.
abstract: 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.
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Jae-Gyu
authors: JG
authors: Kim
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Myoung-Ju
authors: MJ
authors: Kim
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Won-Ji
authors: WJ
authors: Choi
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Mi-Young
authors: MY
authors: Moon
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Hee-Jun
authors: HJ
authors: Kim
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.|Institute of Cell Differentiation and Aging, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Jae-Yong
authors: JY
authors: Lee
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.|Institute of Cell Differentiation and Aging, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Jaebong
authors: J
authors: Kim
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.|Institute of Cell Differentiation and Aging, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Sung-Chan
authors: SC
authors: Kim
authors: Division of Biomedical Convergence, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors: Seung Goo
authors: SG
authors: Kang
authors: Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors: Goo-Young
authors: GY
authors: Seo
authors: Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Kangwon-do, Republic of Korea.
authors: Pyeung-Hyeun
authors: PH
authors: Kim
authors: Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.|Institute of Cell Differentiation and Aging, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.
authors: Jae-Bong
authors: JB
authors: Park
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D060509:Wnt3A Protein / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000577:Amides; D018925:Chemokines; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D060509:Wnt3A Protein; D051176:beta Catenin; C108830:Y 27632; D000071679:Glycogen Synthase Kinase 3 beta; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein