Rac1 augments Wnt signaling by stimulating β-catenin-lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

Cara Jamieson, Christina Lui, Mariana G. Brocardo, Estefania Martino-Echarri, Beric R. Henderson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1- β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin- lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin-LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling.

LanguageEnglish
Pages3933-3946
Number of pages14
JournalJournal of Cell Science
Volume128
Issue number21
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

TCF Transcription Factors
Cell Nucleus Active Transport
beta Catenin
Transcriptional Activation
Ligation
Lymphoid Enhancer-Binding Factor 1
Phosphorylation
Catenins
Wnt Signaling Pathway
Neoplasm Genes
GTP Phosphohydrolases
Immunoprecipitation
Serine
Genes
Up-Regulation
Cell Membrane

Bibliographical note

Copyright 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Jamieson, Cara ; Lui, Christina ; Brocardo, Mariana G. ; Martino-Echarri, Estefania ; Henderson, Beric R. / Rac1 augments Wnt signaling by stimulating β-catenin-lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import. In: Journal of Cell Science. 2015 ; Vol. 128, No. 21. pp. 3933-3946.
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Rac1 augments Wnt signaling by stimulating β-catenin-lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import. / Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

In: Journal of Cell Science, Vol. 128, No. 21, 2015, p. 3933-3946.

Research output: Contribution to journalArticleResearchpeer-review

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