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

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

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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Crossref · 10.1016/s1534-5807(03)00063-7

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45 of 45 references verified0 citation errors · 0 not checkable

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  • Wnt stimulation regulates the stability of Axin, with a de-phosphorylation of Axin and a decrease in cytoplasmic levels of Axin documented.

    “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 [29]

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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
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2003-03
Volume
4
Issue
3
Pages
407-418
ISSN
1534-5807 (ISSN-L)
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
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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