The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow
Abstract
Wnt signalling has an important role in cell fate determination, tissue patterning and tumorigenesis. Secreted antagonists of Wnt include Frizzled (Fz)-related proteins (FRPs), Cerberus, Wnt inhibitory factor (WIF) and Dickkopf (Dkk). FRPs, Cerberus and WIF have all been shown to act by binding and sequestering Wnt. We report a novel mechanism of Wnt-signalling inhibition by human Dkk-1. Dkk-1 demonstrated no interaction with Wnt but bound a single cell surface site with high affinity (K(D) = 0.39 nM). Its receptor was detectable in a complex with a relative molecular mass of 240,000 (M(r) 240K) with [(125)I] Dkk-1 by covalent affinity cross-linking. Wnt signalling through beta-catenin is mediated by the Fz receptor and a recently identified low-density-lipoprotein-receptor-related co-receptor, LRP6/Arrow. Overproduction of the 200K LRP6 protein, but not of Fz, strikingly increased Dkk-1 binding as well as the amount of the 240K cross-linked complex, which was shown to be composed of Dkk-1 and LRP6. Moreover, Dkk-1 function was completely independent of Fz but LRP6 dramatically interfered with the Dkk-1 inhibition of Wnt signalling. Thus, unlike Wnt antagonists, which exert their effects by molecular mimicry of Fz or Wnt sequestration through other mechanisms, Dkk-1 specifically inhibits canonical Wnt signalling by binding to the LRP6 component of the receptor complex.
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“When comparing Fig 6 and S1 Fig, we find that the wet-lab data from just three studies, namely from [105–107], have been reused by simulation studies.”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [105]
In the citing paper
“A second cluster forms around the simulation studies [45, 46, 51, 56, 57] and either includes the same wet-lab data from [105, 106], the Cell cycle [46] or ROS [51, 57].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [105]
In the citing paper
“DKK1 is a high-affinity ligand for LRP6 (Wu et al., 2000;Bafico et al., 2001;Bo et al., 2001;Semenov et al., 2001;Brott and Sokol, 2002) and a member of the dickkopf gene family which including DKK1, DKK2, DKK3 and DKK4.”
From Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding (2005) · cites this paper as Bafico et al., 2001
Citations
Cites
Cell Signaling by Receptor Tyrosine Kinases
Schlessinger, J. (2000) · Cell · doi:10.1016/s0092-8674(00)00114-8 · Cited by 3,774
Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183
Wnt signaling: a common theme in animal development
Cadigan, K. M., & Nusse, R. (1997) · Genes & Development · doi:10.1101/gad.11.24.3286 · Cited by 2,567
Identification of the Hepatocyte Growth Factor Receptor As the c- met Proto-Oncogene Product
Bottaro, D. P., Rubin, J. S., Faletto, D. L., Chan, A. M.-L., Kmiecik, T. E., Woude, G. F. V., & Aaronson, S. A. (1991) · Science · doi:10.1126/science.1846706 · Cited by 2,226
Self-citationDickkopf-1 is a member of a new family of secreted proteins and functions in head induction
Glinka, A., Wu, W., Delius, H., Monaghan, A. P., Blumenstock, C., & Niehrs, C. (1998) · Nature · doi:10.1038/34848 · Cited by 1,608
Linking Colorectal Cancer to Wnt Signaling
Bienz, M., & Clevers, H. C. (2000) · Cell · doi:10.1016/s0092-8674(00)00122-7 · Cited by 1,518
A new member of the frizzled family from Drosophila functions as a Wingless receptor
Bhanot, P., van den Brink, M. R. M., Samos, C. H., Hsieh, J.-C., Wang, Y., Macke, J. P., Andrew, D. J., Nathans, J., & Nusse, R. (1996) · Nature · doi:10.1038/382225a0 · Cited by 1,504
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
Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor
Hannum, C. H., Wilcox, C. J., Arend, W. P., Joslin, F. G., Dripps, D. J., Heimdal, P. L., Armes, L. G., Sommer, A., Eisenberg, S. P., & Thompson, R. C. (1990) · Nature · doi:10.1038/343336a0 · Cited by 1,122
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
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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
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235
Secreted antagonists of the Wnt signalling pathway
Kawano, Y., & Kypta, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00623 · Cited by 1,584
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., & Lifton, R. P. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa013444 · Cited by 1,591
Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.055 · Cited by 1,377
Metadata
- Authors
- Bafico, A., Liu, G., Yaniv, A., Gazit, A., & Aaronson, S. A.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Tel Aviv University (IL)
- Corresponding author
- Aaronson, Stuart A.
- Venue
- Nature Cell Biology
- Published
- 2001-06-12
- Volume
- 3
- Issue
- 7
- Pages
- 683-686
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1557541313
- Cited by
- 772
- References
- 27
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 7 · 2023: 26 · 2022: 26 · 2021: 34 · 2020: 27 · 2019: 20 · 2018: 32 · 2017: 37 · 2016: 37 · 2015: 39 · 2014: 34 · 2013: 33 · 2012: 51
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA071672, CA71672-04)
- 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 › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt signaling, DKK1, LRP6, arrows, Wnt antagonists, Frizzled receptors, β-catenin, receptor complex, ligand binding, cell surface receptors
- MeSH terms
- Cell Line, Cytoskeletal Proteins, Drug Interactions, Humans, Kinetics, Protein Binding, Proteins, Proto-Oncogene Proteins, Receptors, LDL, Transfection, Immunoblotting, Signal Transduction, Trans-Activators, Zebrafish Proteins, Intercellular Signaling Peptides and Proteins, Wnt Proteins, beta Catenin, Low Density Lipoprotein Receptor-Related Protein-6
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