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).
Tamai, K, Zeng, X, Semenov, M, He, X
MacDonald, BT, Tamai, K, Yokota, C, Zeng, X, He, X
Tamai, K, Woodgett, J, Okamura, H, Doble, B, Li, S, Huang, H, Zeng, X, He, X, Habas, R
Zhang, X, Tamai, K, Chang, Z, Harada, Y, Zeng, X, He, X, Liu, C
protein serine/threonine kinase activity of WNT:FZD:LRP5/6:DVL:AXIN:GSK3B [plasma membrane]
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