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Sci. Signal., 15 May 2012
Vol. 5, Issue 224, p. pe22
[DOI: 10.1126/scisignal.2003028]

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The Structural Basis of DKK-Mediated Inhibition of Wnt/LRP Signaling

Ju Bao1, Jie J. Zheng1*, and Dianqing Wu2*

1 Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
2 Department of Pharmacology and Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract: Low-density lipoprotein receptor–related proteins 5 and 6 (LRP5/6) mediate canonical Wnt–β-catenin signaling by forming a complex with the co-receptor Frizzled, which binds to Wnt proteins. Dickkopf (DKK)–related proteins inhibit the Wnt signaling pathway by directly binding to the ectodomains of LRP5/6. However, the mechanism for DKK-mediated antagonism has not been fully understood as of yet. Crystal structures of the LRP6 ectodomain in complex with DKK1, along with mutagenesis studies, provide considerable insights into the molecular basis for DKK-mediated inhibition and Wnt signaling through LRP5/6.

* Corresponding authors. E-mail: jie.zheng{at}stjude.org (J.J.Z.); dan.wu{at}yale.edu (D.W.)

Citation: J. Bao, J. J. Zheng, D. Wu, The Structural Basis of DKK-Mediated Inhibition of Wnt/LRP Signaling. Sci. Signal. 5, pe22 (2012).

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