WNT binds to FZD and LRP5/6

Stable Identifier
R-HSA-1458875
Type
Reaction [binding]
Species
Homo sapiens
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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
22653731 Structural basis of Wnt recognition by Frizzled

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

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

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

Curr Biol 2001
23791946 structural Studies of Wnts and identification of an LRP6 binding site

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

Structure 2013
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

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

Growth Factors 2013
11357136 LDL-receptor-related protein 6 is a receptor for Dickkopf proteins

Wu, W, Niehrs, C, Stannek, P, Mao, B, Li, Y, Hoppe, D, Glinka, A

Nature 2001
15459103 Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP

Schweizer, L, Cong, F, Varmus, H

Development 2004
11029007 LDL-receptor-related proteins in Wnt signal transduction

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

Nature 2000
15084453 LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way

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

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

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

Dev. Cell 2011
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