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

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

Stable Identifier

R-HSA-201677

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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

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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