The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway
Open accessAbstract
To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.
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“The canonical Wnt signalling pathway is mainly involved in cell proliferation and survival in vital biological processes, including organogenesis and embryogenesis.1,2”
From Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function (2024) · cites this paper as [1]
In the citing paper
“The binding of Wnt to the Fz/LRP5/6 complex induces the membrane translocation of a key negative regulator of signaling Axin, which binds to a conserved sequence in the cytoplasmic tail of LRP5/6.27,28”
From Wnt signal transduction pathways (2008) · cites this paper as [27]
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“Because LRP can interact with the cytosolic protein Axin (Mao et al. 2001b, Tolwinski et al. 2003) (Figures 2 and 3), Wnts are thought to induce the phosphorylation of LRP on a PPP(S/T)P motif, thus allowing the docking of Axin to the LRP cytoplasmic tail.”
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Metadata
- Authors
- Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., & Wu, D.
- Affiliations
- University of Connecticut (US)
- Chinese Academy of Sciences (CN)
- University of Washington (US)
- University of Rochester Medicine (US)
- Setsunan University (JP)
- Corresponding author
- Wu, Dianqing
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 7
- Issue
- 4
- Pages
- 801-809
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2152769008
- Cited by
- 839
- References
- 32
- Citations by year
- 2026: 1 · 2025: 15 · 2024: 20 · 2023: 23 · 2022: 25 · 2021: 21 · 2020: 25 · 2019: 25 · 2018: 25 · 2017: 27 · 2016: 23 · 2015: 30 · 2014: 37 · 2013: 46 · 2012: 40
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29gm053162-04)
- National Cancer Institute (R01CA085420, CA85420)
- National Institute of General Medical Sciences (GM53162, GM54167)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD027262, HD27262)
- 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 › Hedgehog Signaling Pathway Studies
- Keywords
- low-density lipoprotein receptor-related protein 5, Axin, Wnt/β-catenin signaling, β-catenin stabilization, protein-protein interaction
- MeSH terms
- Amino Acid Sequence, Animals, Mammals, Molecular Sequence Data, Protein Binding, Proteins, Proto-Oncogene Proteins, Receptors, LDL, Repressor Proteins, Signal Transduction, Gene Expression, Mutagenesis, 3T3 Cells, Protein Structure, Tertiary, Calcium-Calmodulin-Dependent Protein Kinases, COS Cells, LDL-Receptor Related Proteins, Zebrafish Proteins, Glycogen Synthase Kinase 3, Wnt Proteins, Mice, Axin Protein, Low Density Lipoprotein Receptor-Related Protein-5
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