Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling.
Cell
; 133(2): 340-53, 2008 Apr 18.
Article
en En
| MEDLINE
| ID: mdl-18423204
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neuropéptidos
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Transducción de Señal
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Núcleo Celular
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Proteínas de Unión al GTP rac
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Beta Catenina
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos