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Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.

Publication ,  Journal Article
Wu, X; Tu, X; Joeng, KS; Hilton, MJ; Williams, DA; Long, F
Published in: Cell
April 18, 2008

Canonical Wnt signaling critically regulates cell fate and proliferation in development and disease. Nuclear localization of beta-catenin is indispensable for canonical Wnt signaling; however, the mechanisms governing beta-catenin nuclear localization are not well understood. Here we demonstrate that nuclear accumulation of beta-catenin in response to Wnt requires Rac1 activation. The role of Rac1 depends on phosphorylation of beta-catenin at Ser191 and Ser605, which is mediated by JNK2 kinase. Mutations of these residues significantly affect Wnt-induced beta-catenin nuclear accumulation. Genetic ablation of Rac1 in the mouse embryonic limb bud ectoderm disrupts canonical Wnt signaling and phenocopies deletion of beta-catenin in causing severe truncations of the limb. Finally, Rac1 interacts genetically with beta-catenin and Dkk1 in controlling limb outgrowth. Together these results uncover Rac1 activation and subsequent beta-catenin phosphorylation as a hitherto uncharacterized mechanism controlling canonical Wnt signaling and may provide additional targets for therapeutic intervention of this important pathway.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 18, 2008

Volume

133

Issue

2

Start / End Page

340 / 353

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • beta Catenin
  • Wnt3 Protein
  • Wnt Proteins
  • Signal Transduction
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases
  • Neuropeptides
 

Citation

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Wu, X., Tu, X., Joeng, K. S., Hilton, M. J., Williams, D. A., & Long, F. (2008). Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell, 133(2), 340–353. https://doi.org/10.1016/j.cell.2008.01.052
Wu, Ximei, Xiaolin Tu, Kyu Sang Joeng, Matthew J. Hilton, David A. Williams, and Fanxin Long. “Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.Cell 133, no. 2 (April 18, 2008): 340–53. https://doi.org/10.1016/j.cell.2008.01.052.
Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008 Apr 18;133(2):340–53.
Wu, Ximei, et al. “Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.Cell, vol. 133, no. 2, Apr. 2008, pp. 340–53. Pubmed, doi:10.1016/j.cell.2008.01.052.
Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008 Apr 18;133(2):340–353.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 18, 2008

Volume

133

Issue

2

Start / End Page

340 / 353

Location

United States

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • beta Catenin
  • Wnt3 Protein
  • Wnt Proteins
  • Signal Transduction
  • Phosphorylation
  • Phosphatidylinositol 3-Kinases
  • Neuropeptides