Phosphorylation of LRP5/6 cytoplasmic domain by membrane-associated GSK3beta

Stable Identifier
R-HSA-201677
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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LRP5/6 contains 5 PPP(S/T)PxS motifs in its intracellular domain which have been shown to be phosphorylated by a membrane-associated pool of GSK3beta. Individual phosphorylation of each of these motifs promotes interaction with AXIN and stimulates WNT signaling as assessed by activation of a TCF/beta-catenin responsive reporter (Tamai et al, 2004; Zeng et al, 2005; MacDonald et al, 2008). In the context of full length LRP6, phosphorylation of the five motifs shows cooperative stimulation of AXIN binding and WNT signaling. GSK3beta-mediated phosphorylation of LRP6 is thought to prime the receptor for subsequent phosphorylation by CSNK1 (Zeng et al, 2005; reviewed in He et al, 2004).

Literature References
PubMed ID Title Journal Year
18362152 Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6

MacDonald, BT, Yokota, C, Tamai, K, Zeng, X, He, X

J Biol Chem 2008
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
16341017 A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation

Zeng, X, Tamai, K, Doble, B, Li, S, Huang, H, Habas, R, Okamura, H, Woodgett, J, He, X

Nature 2005
14731402 A mechanism for Wnt coreceptor activation

Tamai, K, Zeng, X, Liu, C, Zhang, X, Harada, Y, Chang, Z, He, X

Mol Cell 2004
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Catalyst Activity
Title
protein serine/threonine kinase activity of WNT:FZD:LRP5/6:DVL:AXIN:GSK3B [plasma membrane]
Physical Entity
Activity
Orthologous Events
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