WNT binds to FZD and LRP5/6

Stable Identifier
R-HSA-1458875
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane, cytosol, extracellular region
ReviewStatus
5/5
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WNT binds to FZD and LRP5/6
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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
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
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
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
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
WIF1:WNT [extracellular region] (Homo sapiens)
Active Unit
WIF1 [extracellular region]
Regulator
SOST:LRP5/6 [plasma membrane] (Homo sapiens)
Active Unit
SOST [extracellular region]
Regulator
KRM:DKK:LRP5/6 [plasma membrane] (Homo sapiens)
Regulator
WNT3A:sFRP [extracellular region] (Homo sapiens)
Active Unit
sFRP [extracellular region]
Inferred From
mFz8CRD binds LRP6N in vitro (Homo sapiens)
Authored
Rothfels, K  (2013-05-30)
Reviewed
Rajakulendran, N  (2014-01-22)
van Amerongen, R  (2014-02-15)
Kikuchi, A  (2014-04-22)
Created
Rothfels, K  (2011-07-23)
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