The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling
Open accessAbstract
The Wnt/β-catenin signaling system plays essential roles in embryonic development and in the self-renewal and maintenance of adult stem cells. R-spondins (RSPOs) are a group of secreted proteins that enhance Wnt/β-catenin signaling and have pleiotropic functions in development and stem cell growth. LGR5, an orphan receptor of the G protein-coupled receptor (GPCR) superfamily, is specifically expressed in stem cells of the intestinal crypt and hair follicle. Knockout of LGR5 in the mouse results in neonatal lethality. LGR4, a receptor closely related to LGR5, also has essential roles in development, as its knockout leads to reduced viability and retarded growth. Overexpression of both receptors has been reported in several types of cancer. Here we demonstrate that LGR4 and LGR5 bind the R-spondins with high affinity and mediate the potentiation of Wnt/β-catenin signaling by enhancing Wnt-induced LRP6 phosphorylation. Interestingly, neither receptor is coupled to heterotrimeric G proteins or to β-arrestin when stimulated by the R-spondins, indicating a unique mechanism of action. The findings provide a basis for stem cell-specific effects of Wnt/β-catenin signaling and for the broad range of functions LGR4, LGR5, and the R-spondins have in normal and malignant growth.
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Cites
Identification of stem cells in small intestine and colon by marker gene Lgr5
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Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts
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Intestinal polyposis in mice with a dominant stable mutation of the beta -catenin gene
Harada, N. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.5931 · Cited by 1,212
Lgr5 marks cycling, yet long-lived, hair follicle stem cells
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Zebrafish Prickle, a Modulator of Noncanonical Wnt/Fz Signaling, Regulates Gastrulation Movements
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Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation
Bilić, J., Huang, Y.-L., Davidson, G., Zimmermann, T., Cruciat, C.-M., Bienz, M., & Niehrs, C. (2007) · Science · doi:10.1126/science.1137065 · Cited by 934
Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche
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Wnt Signaling Requires Sequestration of Glycogen Synthase Kinase 3 inside Multivesicular Endosomes
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Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium
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Cited by
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Nusse, R., & Clevers, H. (2017) · Cell · doi:10.1016/j.cell.2017.05.016 · Cited by 4,342
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408
WNT signaling in bone homeostasis and disease: From human mutations to treatments
Baron, R., & Kneissel, M. (2013) · Nature Medicine · doi:10.1038/nm.3074 · Cited by 2,093
Targeting cancer stem cell pathways for cancer therapy
Yang, L., Shi, P., Zhao, G., Xu, J., Peng, W., Zhang, J., Zhang, G., Wang, X., Dong, Z., Chen, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0110-5 · Cited by 1,906
Metadata
- Authors
- Carmon, K. S., Gong, X., Lin, Q., Thomas, A., & Liu, Q.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-06-21
- Volume
- 108
- Issue
- 28
- Pages
- 11452-11457
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2104176068
- Cited by
- 855
- References
- 33
- FWCI
- 26.33
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling. https://app.cochat.ai/papers/10.1073/pnas.1106083108
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- Carmon, K. S., Gong, X., Lin, Q., Thomas, A., & Liu, Q. (2011). R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1106083108
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