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