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

Stable Identifier
Reaction [transition]
Homo sapiens
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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
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
18362152 Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6

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

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

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

Nature 2005
14731402 A mechanism for Wnt coreceptor activation

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

Mol Cell 2004
Catalyst Activity

protein serine/threonine kinase activity of WNT:FZD:LRP5/6:DVL:AXIN:GSK3B [plasma membrane]

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