Phosphorylation of LRP5/6 cytoplasmic domain by CSNKI

Stable Identifier
Reaction [transition]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
11336703 Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway

Li, L, Kimelman, D, Takada, S, Wu, D, Yuan, H, Farr GH, 3rd, Flynn, C, Pan, W, Liu, B, Wang, J, Mao, J

Mol Cell 2001
16341016 Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction

Stannek, P, Wu, W, Niehrs, C, Shen, J, Bilic, J, Fenger, U, Davidson, G, Glinka, A

Nature 2005
17569865 Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation

Niehrs, C, Cruciat, CM, Bienz, M, Zimmermann, T, Huang, YL, Bilic, J, Davidson, G

Science 2007
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
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 CSNK1G2 [plasma membrane]

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