Meta-Biol

• Pathways

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).