After being phosphorylated by GSK3beta on the PPPSP motifs, LRP6 (and by extension LRP5) is phosphorylated at up to 5 sites by a member of the CSNK1 family (Davidson et al, 2005). One screen identified CSNK1gamma as a candidate kinase, while another study showed that CSNK1alpha, delta and epsilon contribute to this phosphorylation step (Davidson et al, 2005; Zeng et al, 2005). This sequential phosphorylation of LRP5/6 by GSK3beta and CSNK1 generates a high affinity binding site for AXIN, thereby amplifying the recruitment of AXIN to the membrane. This is thought to promote the disassembly of the destruction complex, and the activation of WNT signaling (Mao et al, 2001; Tamai et al, 2004; Bilic et al, 2007; reviewed in He et al, 2004).
Li, L, Kimelman, D, Takada, S, Wu, D, Yuan, H, Farr GH, 3rd, Flynn, C, Pan, W, Liu, B, Wang, J, Mao, J
Stannek, P, Wu, W, Niehrs, C, Shen, J, Bilic, J, Fenger, U, Davidson, G, Glinka, A
Niehrs, C, Cruciat, CM, Bienz, M, Zimmermann, T, Huang, YL, Bilic, J, Davidson, G
Tamai, K, Zeng, X, Semenov, M, 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 CSNK1G2 [plasma membrane]
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