The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
1 retracted
Chan, S.-K., & Struhl, G. (2002) · Cell · doi:10.1016/s0092-8674(02)01037-1 · Cited by 58
RetractedTargeted gene expression as a means of altering cell fates and generating dominant phenotypes
Brand, A. H., & Perrimon, N. (1993) · Development · doi:10.1242/dev.118.2.401 · Cited by 9,510
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Liu, C., Li, Y., Semënov, M. V., Han, C., Baeg, G., Tan, Y., Zhang, Z., Lin, X., & He, X. (2002) · Cell · doi:10.1016/s0092-8674(02)00685-2 · Cited by 2,152
MECHANISMS OF WNT SIGNALING IN DEVELOPMENT
Wodarz, A., & Nusse, R. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.59 · Cited by 2,030
Molecular cloning and expression of glycogen synthase kinase‐3/factor A.
Woodgett, J. R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07419.x · Cited by 1,362
LDL-receptor-related proteins in Wnt signal transduction
Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P., & He, X. (2000) · Nature · doi:10.1038/35035117 · Cited by 1,128
An LDL-receptor-related protein mediates Wnt signalling in mice
Pinson, K. I., Brennan, J., Monkley, S. J., Avery, B. J., & Skarnes, W. C. (2000) · Nature · doi:10.1038/35035124 · Cited by 1,086
LDL-receptor-related protein 6 is a receptor for Dickkopf proteins
Mao, B., Wu, W., Li, Y., Hoppe, D., Stannek, P., Glinka, A., & Niehrs, C. (2001) · Nature · doi:10.1038/35077108 · Cited by 1,042
Zeng, L., Fagotto, F., Zhang, T., Hsu, W., Vasicek, T. J., Perry, W. L., Lee, J. J., Tilghman, S. M., Gumbiner, B. M., & Costantini, F. D. (1997) · Cell · doi:10.1016/s0092-8674(00)80324-4 · Cited by 907
arrow encodes an LDL-receptor-related protein essential for Wingless signalling
Wehrli, M., Dougan, S. T., Caldwell, K. A., O’Keefe, L. V., Schwartz, S. L., Vaizel-Ohayon, D., Schejter, E. D., Tomlinson, A., & DiNardo, S. (2000) · Nature · doi:10.1038/35035110 · Cited by 871
Self-citationMao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., et al. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00224-6 · Cited by 839
Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathwayPreprint
Amit, S., Hatzubai, A., Birman, Y., Andersen, J., Ben-Shushan, E., Mann, M., Ben‐Neriah, Y., & Alkalay, I. (2002) · Genes & Development · doi:10.1101/gad.230302 · Cited by 784
Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6
Semënov, M. V., Tamai, K., Brott, B. K., Kühl, M., Sokol, S., & He, X. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00290-1 · Cited by 616
β-catenin translocation into nuclei demarcates the dorsalizing centers in frog and fish embryos
Schneider, S., Steinbeißer, H., Warga, R. M., & Hausen, P. (1996) · Mechanisms of Development · doi:10.1016/0925-4773(96)00546-1 · Cited by 515
Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila.
Chou, T.-B., & Perrimon, N. (1992) · Genetics · doi:10.1093/genetics/131.3.643 · Cited by 493
Nuclear-cytoplasmic shuttling of APC regulates β-catenin subcellular localization and turnover
Henderson, B. R. (2000) · Nature Cell Biology · doi:10.1038/35023605 · Cited by 483
Nuclear β-catenin is required to specify vegetal cell fates in the sea urchin embryo
Logan, C. Y., Miller, J. R., Ferkowicz, M. J., & McClay, D. R. (1999) · Development · doi:10.1242/dev.126.2.345 · Cited by 456
Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways
Novak, A., Hsu, S.-C., Leung-Hagesteijn, C., Radeva, G., Papkoff, J., Montesano, R., Roskelley, C. D., Grosschedl, R., & Dedhar, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4374 · Cited by 434
Peifer, M. A., Sweeton, D., Casey, M. J., & Wieschaus, E. F. (1994) · Development · doi:10.1242/dev.120.2.369 · Cited by 426
Self-citationSiegfried, E., Chou, T.-B., & Perrimon, N. (1992) · Cell · doi:10.1016/s0092-8674(05)80065-0 · Cited by 423
Arias, A. M., Baker, N. E., & Ingham, P. W. (1988) · Development · doi:10.1242/dev.103.1.157 · Cited by 384
Price, M. A., & Kalderon, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00664-5 · Cited by 381
Yamamoto, H., Kishida, S., Kishida, M., Ikeda, S., Takada, S., & Kikuchi, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10681 · Cited by 364
Uncoupling cadherin-based adhesion from wingless signalling in Drosophila
Sanson, B., White, P., & Vincent, J. (1996) · Nature · doi:10.1038/383627a0 · Cited by 360
The APC tumour suppressor has a nuclear export function
Rosin-Arbesfeld, R., Townsley, F., & Bienz, M. (2000) · Nature · doi:10.1038/35023016 · Cited by 343
Wnt-induced dephosphorylation of Axin releases beta -catenin from the Axin complexPreprint
Willert, K., Shibamoto, S., & Nusse, R. (1999) · Genes & Development · doi:10.1101/gad.13.14.1768 · Cited by 337
Control of β-Catenin Stability
Salic, A., Lee, E., Mayer, L., & Kirschner, M. W. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80446-3 · Cited by 335
Components of wingless signalling in Drosophila
Siegfried, E., Wilder, E. L., & Perrimon, N. (1994) · Nature · doi:10.1038/367076a0 · Cited by 329
Shaggy/GSK3 antagonizes Hedgehog signalling by regulating Cubitus interruptus
Jia, J., Amanai, K., Wang, G., Tang, J., Wang, B., & Jiang, J. (2002) · Nature · doi:10.1038/nature733 · Cited by 288
Peifer, M. A., Pai, L., & Casey, M. J. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1336 · Cited by 249
Presenilin Couples the Paired Phosphorylation of β-Catenin Independent of Axin
Kang, D. E., Soriano, S., Xia, X., Eberhart, C. G., Strooper, B. D., Zheng, H., & Koo, E. H. (2002) · Cell · doi:10.1016/s0092-8674(02)00970-4 · Cited by 236
Regulation of Armadillo by a Drosophila APC Inhibits Neuronal Apoptosis during Retinal Development
Ahmed, Y. F., Hayashi, S., Levine, A. J., & Wieschaus, E. F. (1998) · Cell · doi:10.1016/s0092-8674(00)81461-0 · Cited by 223
Self-citationRuel, L., Bourouis, M., Heitzler, P., Pantesco, V., & Simpson, P. (1993) · Nature · doi:10.1038/362557a0 · Cited by 202
Negative Regulation of Wingless Signaling by D-Axin, a Drosophila Homolog of Axin
Hamada, F., Tomoyasu, Y., Takatsu, Y., Nakamura, M., Nagai, S.-I., Suzuki, A., Fujita, F., Shibuyà, H., Toyoshima, K., Ueno, N., et al. (1999) · Science · doi:10.1126/science.283.5408.1739 · Cited by 199
Wingless transduction by the Frizzled and Frizzled2 proteins of Drosophila
Chen, C. M., & Struhl, G. (1999) · Development · doi:10.1242/dev.126.23.5441 · Cited by 193
Li, L., Mao, J., Sun, L., Liu, W., & Wu, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111131200 · Cited by 168
Bhanot, P., Fish, M., Jemison, J. A., Nusse, R., Nathans, J., & Cadigan, K. M. (1999) · Development · doi:10.1242/dev.126.18.4175 · Cited by 163
Casein Kinase 1: A Wnt'er of Disconnect
Polakis, P. G. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00969-7 · Cited by 154
A Drosophila Axin homolog, Daxin, inhibits Wnt signaling
Willert, K., Logan, C. Y., Arora, A., Fish, M., & Nusse, R. (1999) · Development · doi:10.1242/dev.126.18.4165 · Cited by 117
Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan
Tolwinski, N. S., & Wieschaus, E. F. (2001) · Development · doi:10.1242/dev.128.11.2107 · Cited by 109
Self-citationDrosophila α-Catenin and E-cadherin Bind to Distinct Regions of Drosophila Armadillo
Pai, L., Kirkpatrick, C. A., Blanton, J. L., Oda, H., Takeichi, M., & Peifer, M. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32411 · Cited by 102
DrosophilaApc1 and Apc2 regulate Wingless transduction throughout development
Ahmed, Y. F., Nouri, A., & Wieschaus, E. F. (2002) · Development · doi:10.1242/dev.129.7.1751 · Cited by 93
Self-citationFunctional significance of a family of protein kinases encoded at the shaggy locus in Drosophila.
Ruel, L., Pantesco, V., Lutz, Y., Simpson, P., & Bourouis, M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05811.x · Cited by 68
Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization
Luo, L., Lee, T., Tsai, L. T.-Y., Tang, G. L., Jan, L. Y., & Jan, Y. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12963 · Cited by 68
Wingless signaling generates pattern through two distinct mechanisms
Hays, R., Gibori, G. B., & Bejsovec, A. (1997) · Development · doi:10.1242/dev.124.19.3727 · Cited by 63
Cited by
Sorted by citations
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
“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.”
BackgroundWnt signal transduction pathways
Komiya, Y., & Habas, R. (2008) · Organogenesis · doi:10.4161/org.4.2.5851 · Cited by 1,528
Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors
Gordon, M. D., & Nusse, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.r600015200 · Cited by 1,333
The -Catenin Destruction Complex
Stamos, J. L., & Weis, W. I. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007898 · Cited by 1,062
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
