Cited by 364Wnt/β-catenin signaling in development and cancerSignaling Pathways in DiseaseFOXO transcription factor regulation

Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3β Regulates Its Stability

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Yamamoto, Hideki, Kishida, Shosei, Kishida, Michiko, Ikeda, Satoshi, Takada, Shinji, Kikuchi, Akira·1999·Journal of Biological Chemistry

Abstract

Axin forms a complex with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin, thereby stimulating the degradation of beta-catenin. Because GSK-3beta also phosphorylates Axin in the complex, the physiological significance of the phosphorylation of Axin was examined. Treatment of COS cells with LiCl, a GSK-3beta inhibitor, and okadaic acid, a protein phosphatase inhibitor, decreased and increased, respectively, the cellular protein level of Axin. Pulse-chase analyses showed that the phosphorylated form of Axin was more stable than the unphosphorylated form and that an Axin mutant, in which the possible phosphorylation sites for GSK-3beta were mutated, exhibited a shorter half-life than wild type Axin. Dvl-1, which was genetically shown to function upstream of GSK-3beta, inhibited the phosphorylation of Axin by GSK-3beta in vitro. Furthermore, Wnt-3a-containing conditioned medium down-regulated Axin and accumulated beta-catenin in L cells and expression of Dvl-1(DeltaPDZ), in which the PDZ domain was deleted, suppressed this action of Wnt-3a. These results suggest that the phosphorylation of Axin is important for the regulation of its stability and that Wnt down-regulates Axin through Dvl.

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Crossref · 10.1074/jbc.274.16.10681

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  • Wnt stimulation regulates the stability of Axin, with a de-phosphorylation of Axin and a decrease in cytoplasmic levels of Axin documented.

    “It is important to note that Wnt stimulation also regulates the stability of Axin for with Wnt stimulation a de-phosphorylation of Axin and a decrease in cytoplasmic levels of Axin has been documented.29–31”

    From Wnt signal transduction pathways (2008) · cites this paper as [31]

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Authors
Yamamoto, H., Kishida, S., Kishida, M., Ikeda, S., Takada, S., & Kikuchi, A.
Affiliations
  • Hiroshima University (JP)
  • Kyoto University (JP)
Corresponding author
Kikuchi, Akira
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-04
Volume
274
Issue
16
Pages
10681-10684
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2013460988
Cited by
364
References
41
Citations by year
2026: 2 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 6 · 2021: 10 · 2020: 3 · 2019: 8 · 2018: 10 · 2017: 15 · 2016: 12 · 2015: 5 · 2014: 19 · 2013: 13 · 2012: 19
FWCI
8.50
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
Axin, glycogen synthase kinase-3β, protein phosphorylation, protein stability, Wnt signaling, β-catenin degradation, PDZ domain, Wnt3a, protein phosphatase
MeSH terms
Dishevelled Proteins, Animals, Phosphoproteins, Phosphorylation, Proteins, Repressor Proteins, Down-Regulation, Calcium-Calmodulin-Dependent Protein Kinases, COS Cells, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Adaptor Proteins, Signal Transducing, Wnt Proteins, Axin Protein, Wnt3 Protein

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