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

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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

DOI 10.1074/jbc.274.16.10681

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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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Authors: Yamamoto, H., Kishida, S., Kishida, M., Ikeda, S., Takada, S., & Kikuchi, A.
Affiliations: Hiroshima University (JP)
Kyoto University (JP)
Corresponding author: Kikuchi, Akira
ORCID: Yamamoto, Hideki
Kishida, Shosei
Kishida, Michiko
Ikeda, Satoshi
Takada, Shinji
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)
DOI: 10.1074/jbc.274.16.10681
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: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7857 d)
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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Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3β Regulates Its Stability

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