| Autor: |
Jamieson, Cara, Lui, Christina, Brocardo, Mariana G., Martino-Echarri, Estefania, Henderson, Beric R. |
| Předmět: |
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| Zdroj: |
Journal of Cell Science; 2015, Vol. 128 Issue 21, p3933-3946, 14p |
| Abstrakt: |
ß-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate ß-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 ß-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of ß-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1-ß-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 ß-catenin-lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of ß-catenin at specific serines, which when mutated (S191A and S605A) reduced ß-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of ß-catenin stimulates Wnt-dependent gene transactivation by enhancing ß-catenin-LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/ß-catenin signaling. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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