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Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.

de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H.

Nature. 2011 Jul 4;476(7360):293-7. doi: 10.1038/nature10337.


R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling.

Carmon KS, Gong X, Lin Q, Thomas A, Liu Q.

Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11452-7. doi: 10.1073/pnas.1106083108. Epub 2011 Jun 21.


LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling.

Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C.

EMBO Rep. 2011 Sep 30;12(10):1055-61. doi: 10.1038/embor.2011.175.


R-Spondin potentiates Wnt/β-catenin signaling through orphan receptors LGR4 and LGR5.

Ruffner H, Sprunger J, Charlat O, Leighton-Davies J, Grosshans B, Salathe A, Zietzling S, Beck V, Therier M, Isken A, Xie Y, Zhang Y, Hao H, Shi X, Liu D, Song Q, Clay I, Hintzen G, Tchorz J, Bouchez LC, Michaud G, Finan P, Myer VE, Bouwmeester T, Porter J, Hild M, Bassilana F, Parker CN, Cong F.

PLoS One. 2012;7(7):e40976. doi: 10.1371/journal.pone.0040976. Epub 2012 Jul 16.


Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins.

Schuijers J, Clevers H.

EMBO J. 2012 Jun 13;31(12):2685-96. doi: 10.1038/emboj.2012.149. Epub 2012 May 22. Review.


Structure of stem cell growth factor R-spondin 1 in complex with the ectodomain of its receptor LGR5.

Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, Gros P.

Cell Rep. 2013 Jun 27;3(6):1885-92. doi: 10.1016/j.celrep.2013.06.009.


Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression.

Nam JS, Turcotte TJ, Smith PF, Choi S, Yoon JK.

J Biol Chem. 2006 May 12;281(19):13247-57. Epub 2006 Mar 16.


ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner.

Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F.

Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019.


LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor.

Gong X, Carmon KS, Lin Q, Thomas A, Yi J, Liu Q.

PLoS One. 2012;7(5):e37137. doi: 10.1371/journal.pone.0037137. Epub 2012 May 17.


LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/β-catenin signaling.

Carmon KS, Lin Q, Gong X, Thomas A, Liu Q.

Mol Cell Biol. 2012 Jun;32(11):2054-64. doi: 10.1128/MCB.00272-12. Epub 2012 Apr 2.


Structural basis for R-spondin recognition by LGR4/5/6 receptors.

Wang D, Huang B, Zhang S, Yu X, Wu W, Wang X.

Genes Dev. 2013 Jun 15;27(12):1339-44. doi: 10.1101/gad.219360.113. Epub 2013 Jun 11.


The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength.

de Lau W, Peng WC, Gros P, Clevers H.

Genes Dev. 2014 Feb 15;28(4):305-16. doi: 10.1101/gad.235473.113. Review.


Stem cells: Orphan receptors find a home.

Birchmeier W.

Nature. 2011 Aug 17;476(7360):287-8. doi: 10.1038/476287a. No abstract available.


Structures of Wnt-antagonist ZNRF3 and its complex with R-spondin 1 and implications for signaling.

Peng WC, de Lau W, Madoori PK, Forneris F, Granneman JC, Clevers H, Gros P.

PLoS One. 2013 Dec 12;8(12):e83110. doi: 10.1371/journal.pone.0083110. eCollection 2013.


Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

Xu JG, Huang C, Yang Z, Jin M, Fu P, Zhang N, Luo J, Li D, Liu M, Zhou Y, Zhu Y.

J Biol Chem. 2015 Jan 23;290(4):2455-65. doi: 10.1074/jbc.M114.599134. Epub 2014 Dec 5.


The structural basis of R-spondin recognition by LGR5 and RNF43.

Chen PH, Chen X, Lin Z, Fang D, He X.

Genes Dev. 2013 Jun 15;27(12):1345-50. doi: 10.1101/gad.219915.113. Epub 2013 Jun 11.


Reconstitution of R-spondin:LGR4:ZNRF3 adult stem cell growth factor signaling complexes with recombinant proteins produced in Escherichia coli.

Moad HE, Pioszak AA.

Biochemistry. 2013 Oct 15;52(41):7295-304. doi: 10.1021/bi401090h. Epub 2013 Oct 3.


Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis.

Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJ, van de Wetering M, Sojoodi M, Li VS, Schuijers J, Gracanin A, Ringnalda F, Begthel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H, Clevers H.

EMBO J. 2013 Oct 16;32(20):2708-21. doi: 10.1038/emboj.2013.204. Epub 2013 Sep 17.


Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells.

Lyons JP, Mueller UW, Ji H, Everett C, Fang X, Hsieh JC, Barth AM, McCrea PD.

Exp Cell Res. 2004 Aug 15;298(2):369-87.


Lgr4 gene deficiency increases susceptibility and severity of dextran sodium sulfate-induced inflammatory bowel disease in mice.

Liu S, Qian Y, Li L, Wei G, Guan Y, Pan H, Guan X, Zhang L, Lu X, Zhao Y, Liu M, Li D.

J Biol Chem. 2013 Mar 29;288(13):8794-803; discussion 8804. doi: 10.1074/jbc.M112.436204. Epub 2013 Feb 7.

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