WNT binds to FZD and LRP5/6

Stable Identifier
R-HSA-1458875
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The canonical WNT signaling pathway is initiated when WNT ligands bind to the 7 pass transmembrane receptor Frizzled (FZD) proteins (reviewed in Saito-Diaz et al, 2013). The single pass low-density lipoprotein receptor-related protein (LRP) 5/6 membrane proteins are thought to act as co-receptors with FZD proteins for WNTs, although the details are not fully worked out and a FZD:LRP interaction has not been demonstrated with endogenous proteins in vivo (reviewed in He et al, 2004). LRP5/6 have also been shown to bind directly to a subset of WNT proteins, although the data is conflicting (see for instance Tamai et al, 2000; Semenov et al, 2001; Cong et al, 2004; Wu and Nusse, 2002; Mao et al, 2001). Recent crystal structures have demonstrated direct binding of purified WNT proteins to LRP6 and FZD8 in vitro (Ahn et al, 2011; Janda et al, 2012; Chu et al, 2013), but it is not clear whether the LRP and FZD receptors bind WNTs independently, sequentially or cooperatively in vivo (reviewed in He et al, 2004; Saito-Diaz et al, 2013).

Literature References
PubMed ID Title Journal Year
11029007 LDL-receptor-related proteins in Wnt signal transduction

Tamai, K, Semenov, M, Kato, Y, Spokony, R, Liu, C, Katsuyama, Y, Hess, F, Saint-Jeannet, JP, He, X

Nature 2000
23791946 structural Studies of Wnts and identification of an LRP6 binding site

Chu, ML, Ahn, VE, Choi, HJ, Daniels, DL, Nusse, R, Weis, WI

Structure 2013
11357136 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

Nature 2001
12205098 Ligand receptor interactions in the Wnt signaling pathway in Drosophila

Wu, CH, Nusse, R

J Biol Chem 2002
23256519 The way Wnt works: Components and mechanism

Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E

Growth Factors 2013
22653731 Structural basis of Wnt recognition by Frizzled

Janda, CY, Waghray, D, Levin, AM, Thomas, C, Garcia, KC

Science 2012
11448771 Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6

Semënov, MV, Tamai, K, Brott, BK, Kühl, M, Sokol, S, He, X

Curr Biol 2001
15084453 LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way

He, X, Semenov, M, Tamai, K, Zeng, X

Development 2004
15459103 Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP

Cong, F, Schweizer, L, Varmus, H

Development 2004
22000856 Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6

Ahn, VE, Chu, ML, Choi, HJ, Tran, D, Abo, A, Weis, WI

Dev. Cell 2011
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