Cited by 839Wnt/β-catenin signaling in development and cancerSignaling Pathways in DiseaseHedgehog Signaling Pathway Studies

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Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway

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Mao, Junhao, Wang, Jiyong, Liu, Bo, Pan, Weijun, Farr, Gist H, Flynn, Christopher, Yuan, Huidong, Takada, Shinji, Kimelman, David, Li, Lin, Wu, Dianqing·2001·Molecular Cell

DOI 10.1016/s1097-2765(01)00224-6

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Abstract

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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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
ORCID: Mao, Junhao
Liu, Bo
Pan, Weijun
Takada, Shinji
Kimelman, David
Wu, Dianqing
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2001-04
Volume: 7
Issue: 4
Pages: 801-809
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(01)00224-6
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4490 d)
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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Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway

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