Cited by 286Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationHedgehog Signaling Pathway Studies

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Wg/Wnt Signal Can Be Transmitted through Arrow/LRP5,6 and Axin Independently of Zw3/Gsk3β Activity

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Tolwinski, Nicholas S, Wehrli, Marcel, Rives, Anna, Erdeniz, Naz, DiNardo, Stephen, Wieschaus, Eric·2003·Developmental Cell

DOI 10.1016/s1534-5807(03)00063-7

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Abstract

Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3beta/Zw3, the kinase normally required for controlling beta-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.

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Self-citation
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Boulter, L. (2011) · ERA
Role for the Axin-RGS domain during embryonic development
Schneider, P. N. (2010) · doi:10.17077/etd.1lixw2of
“The cytoplasmic domain of Lrp5/6 has been shown to interact with Axin upon Wnt signaling activation (He et al., 2004; Mao et al., 2001; Tolwinski et al., 2003).”
Background

Authors: Tolwinski, N. S., Wehrli, M., Rives, A., Erdeniz, N., DiNardo, S., & Wieschaus, E.
Affiliations: Howard Hughes Medical Institute (US)
Oregon Health & Science University (US)
University of Pennsylvania (US)
Corresponding author: Wieschaus, Eric
ORCID: Tolwinski, Nicholas S
Wehrli, Marcel
DiNardo, Stephen
Wieschaus, Eric
Venue: Developmental Cell
Publisher: Elsevier BV
Published: 2003-03
Volume: 4
Issue: 3
Pages: 407-418
ISSN: 1534-5807 (ISSN-L)
DOI: 10.1016/s1534-5807(03)00063-7
OpenAlex: W2037128138
Cited by: 286
References: 45
Citations by year: 2026: 3 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 14 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 18
FWCI: 9.83
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3791 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Developmental Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (GM45747, PO1CA41086, F32GM20342)
Howard Hughes Medical Institute
National Science Foundation
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 › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
Keywords: Wnt signaling, Axin, GSK3β, Frizzled-2, ligand-independent signaling, Wnt receptors
MeSH terms: Glycogen Synthase Kinase 3 beta, Animals, Carrier Proteins, Drosophila melanogaster, Embryo, Nonmammalian, Female, Membrane Proteins, Mutation, Proto-Oncogene Proteins, Receptors, Cell Surface, Receptors, LDL, Recombinant Fusion Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Gene Expression Regulation, Developmental, Active Transport, Cell Nucleus, LDL-Receptor Related Proteins, Drosophila Proteins, Glycogen Synthase Kinase 3, Receptors, G-Protein-Coupled, Adaptor Proteins, Signal Transducing, Wnt1 Protein, Frizzled Receptors, Armadillo Domain Proteins, Low Density Lipoprotein Receptor-Related Protein-5

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Wg/Wnt Signal Can Be Transmitted through Arrow/LRP5,6 and Axin Independently of Zw3/Gsk3β Activity

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