Low-density lipoprotein receptor-related protein 6

Definition:

Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).

References:

[1]. B Mao, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001 May 17;411(6835):321-5. [Content Brief]

[2]. M V Semënov, et al. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001 Jun 26;11(12):951-61. [Content Brief]

[3]. Xin Zeng, et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005 Dec 8;438(7069):873-7. [Content Brief]

[4]. Xiaofeng Li, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005 May 20;280(20):19883-7. [Content Brief]

[5]. Minyong Chen, et al. G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009 Dec 11;284(50):35040-8. [Content Brief]

[6]. Kaihong Mi, et al. Regulated proteolytic processing of LRP6 results in release of its intracellular domain. J Neurochem. 2007 Apr;101(2):517-29. [Content Brief]

[7]. Wojciech Swiatek, et al. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. J Biol Chem. 2006 May 5;281(18):12233-41. [Content Brief]

[8]. Geng Wu, et al. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One. 2009;4(3):e4926. [Content Brief]

[9]. Shunfu Piao, et al. Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS One. 2008;3(12):e4046. [Content Brief]

[10]. Qiou Wei, et al. R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J Biol Chem. 2007 May 25;282(21):15903-11. [Content Brief]

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