A Role of Dishevelled in Relocating Axin to the Plasma Membrane during Wingless Signaling

Wnt signaling causes changes in gene transcription that are pivotal for normal and malignant development [1, 2]. A key effector of the canonical Wnt pathway is β-catenin, or Drosophila Armadillo. In the absence of Wnt ligand, β-catenin is phosphorylated by the Axin complex, which earmarks it for rap...

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Bibliographic Details
Published in:Current biology 2003-05, Vol.13 (11), p.960-966
Main Authors: Cliffe, Adam, Hamada, Fumihiko, Bienz, Mariann
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Axin Protein
Blotting, Western
Carrier Proteins - metabolism
Cell Membrane - metabolism
Dishevelled Proteins
Drosophila - genetics
Drosophila Proteins - metabolism
Fluorescent Antibody Technique
Green Fluorescent Proteins
Luminescent Proteins
Phosphoproteins - metabolism
Proto-Oncogene Proteins - metabolism
Signal Transduction
Wnt1 Protein
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Summary:Wnt signaling causes changes in gene transcription that are pivotal for normal and malignant development [1, 2]. A key effector of the canonical Wnt pathway is β-catenin, or Drosophila Armadillo. In the absence of Wnt ligand, β-catenin is phosphorylated by the Axin complex, which earmarks it for rapid degradation by the ubiquitin system. Axin acts as a scaffold in this complex, to assemble β-catenin substrate and kinases (casein kinase I [CKI] and glycogen synthase kinase 3β [GSK3]) [3, 4]. The Adenomatous polyposis coli (APC) tumor suppressor also binds to the Axin complex, thereby promoting the degradation of β-catenin [5, 6]. In Wnt signaling, this complex is inhibited; as a consequence, β-catenin accumulates and binds to TCF proteins to stimulate the transcription of Wnt target genes [1, 2]. Wnt-induced inhibition of the Axin complex depends on Dishevelled (Dsh) [7–9], a cytoplasmic protein that can bind to Axin [10, 11], but the mechanism of this inhibition is not understood. Here, we show that Wingless signaling causes a striking relocation of Drosophila Axin from the cytoplasm to the plasma membrane. This relocation depends on Dsh. It may permit the subsequent inactivation of the Axin complex by Wingless signaling.
ISSN:0960-9822
1879-0445
DOI:10.1016/S0960-9822(03)00370-1