The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3β Regulates Its Stability
Open accessAbstract
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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“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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Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183
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Metadata
- 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
- hybrid
- doi.org
- Licence
- 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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