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| LRP6SummaryGene Symbol: LRP6 Description: LDL receptor related protein 6 Alias: ADCAD2, STHAG7, low-density lipoprotein receptor-related protein 6, LRP-6 Species: human Products: LRP6 Top Publications
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Publications
- Tanneberger K, Pfister A, Brauburger K, Schneikert J, Hadjihannas M, Kriz V, et al. Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to LRP6 phosphorylation. EMBO J. 2011;30:1433-43 pubmed publisherPhosphorylation of the Wnt receptor low-density lipoprotein receptor-related protein 6 (LRP6) by glycogen synthase kinase 3? (GSK3?) and casein kinase 1? (CK1?) is a key step in Wnt/?-catenin signalling, which requires Wnt-induced ..
- Semenov M, Tamai K, Brott B, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001;11:951-61 pubmed..initiates signaling via the Frizzled (Fz) receptor and its candidate coreceptor, LDL receptor-related protein 6 (LRP6), presumably through Fz-LRP6 complex formation induced by Wnt...
- Lee J, Hur M, Lee S, Choi W, Kwon Y, Yun C. A novel sLRP6E1E2 inhibits canonical Wnt signaling, epithelial-to-mesenchymal transition, and induces mitochondria-dependent apoptosis in lung cancer. PLoS ONE. 2012;7:e36520 pubmed publisher..Taken together, sLRP6E1E2, by inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell proliferation and epithelial-to-mesenchymal transition. ..
- Semenov M, Zhang X, He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem. 2008;283:21427-32 pubmed publisher..DKK1 is a high affinity antagonistic ligand for LRP6, which is a Wnt coreceptor that acts together with the Frizzled serpentine receptor to initiate Wnt signal ..
- Tomaszewski M, Charchar F, Barnes T, Gawron Kiszka M, Sedkowska A, Podolecka E, et al. A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-cholesterol. Arterioscler Thromb Vasc Biol. 2009;29:1316-21 pubmed publisherA rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease...
- Liu C, Pearson C, Bu G. Cooperative folding and ligand-binding properties of LRP6 beta-propeller domains. J Biol Chem. 2009;284:15299-307 pubmed publisher..b>LRP6, the essential co-receptor for the Wnt pathway, consists of four beta-propeller domains flanked by epidermal growth ..
- Chen M, Philipp M, Wang J, Premont R, Garrison T, Caron M, et al. G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway. J Biol Chem. 2009;284:35040-8 pubmed publisher..Subsequently, phosphorylation of serine/threonine residues within five repeating signature PPPSP motifs on LRP6 is responsible for LRP6 activation...
- Binnerts M, Kim K, Bright J, Patel S, Tran K, Zhou M, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007;104:14700-5 pubmed..RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6...
- Sarzani R, Salvi F, Bordicchia M, Guerra F, Battistoni I, Pagliariccio G, et al. Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant. Nutr Metab Cardiovasc Dis. 2011;21:150-6 pubmed publisherRare (611C) and common (1062V) variants of the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) display reduced activation of Wnt/ß-catenin signaling...
- Khan Z, Vijayakumar S, de la Torre T, Rotolo S, Bafico A. Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor. Mol Cell Biol. 2007;27:7291-301 pubmed..The LRP6 single-span transmembrane coreceptor is essential for transmission of canonical Wnt signaling...
- Wu G, Huang H, Garcia Abreu J, He X. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS ONE. 2009;4:e4926 pubmed publisher..On activation by Wnt, the Wnt co-receptor LDL receptor related protein 6 (LRP6) is phosphorylated at multiple conserved intracellular PPPSPXS motifs by glycogen synthase kinase 3 (GSK3) and ..
- Wan M, Yang C, Li J, Wu X, Yuan H, Ma H, et al. Parathyroid hormone signaling through low-density lipoprotein-related protein 6. Genes Dev. 2008;22:2968-79 pubmed publisher..Here we show that binding of PTH to its receptor PTH1R induced association of LRP6, a coreceptor of Wnt, with PTH1R...
- De Ferrari G, Papassotiropoulos A, Biechele T, Wavrant De Vrieze F, Avila M, Major M, et al. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. Proc Natl Acad Sci U S A. 2007;104:9434-9 pubmed..Alzheimer's disease on chromosome 12, which contains the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) gene, a coreceptor for Wnt signaling...
- Yamamoto H, Komekado H, Kikuchi A. Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev Cell. 2006;11:213-23 pubmed..The single-span transmembrane Wnt receptor, low-density lipoprotein receptor-related protein 6 (LRP6), interacts with Axin to promote the Wnt-dependent accumulation of beta-catenin...
- Haines J, Schnetz Boutaud N, Schmidt S, Scott W, Agarwal A, Postel E, et al. Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest Ophthalmol Vis Sci. 2006;47:329-35 pubmed..enzyme [DCP1], interleukin-1alpha [IL1A], low-density lipoprotein receptor-related protein 6 [LRP6], microsomal glutathione-S-transferase 1 [MGST1], vascular entothelial growth factor [VEGF], and very low density ..
- Cervenka I, Wolf J, Masek J, Krejci P, Wilcox W, Kozubik A, et al. Mitogen-activated protein kinases promote WNT/beta-catenin signaling via phosphorylation of LRP6. Mol Cell Biol. 2011;31:179-89 pubmed publisherLDL-related protein 6 (LRP6) is a coreceptor of WNTs and a key regulator of the WNT/?-catenin pathway. Upon activation, LRP6 is phosphorylated within its intracellular PPPS/TP motifs...
- He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004;131:1663-77 pubmed..Low-density-lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) in vertebrates, and their Drosophila ortholog Arrow, are single-span transmembrane proteins that are indispensable ..
- Liang J, Fu Y, Cruciat C, Jia S, Wang Y, Tong Z, et al. Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation. Mol Cell Biol. 2011;31:2577-90 pubmed publisher..Upon Wnt stimulation, cognate coreceptors LRP5 and LRP6 ([LRP5/6] low-density lipoprotein receptor-related proteins 5 and 6) are activated via phosphorylation at key ..
- Holmen S, Salic A, Zylstra C, Kirschner M, Williams B. A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling. J Biol Chem. 2002;277:34727-35 pubmed..In 293T cells, coexpression of several Wnt-Fz fusion proteins with LRP6, but not LRP5, significantly activated a Wnt-responsive promoter, Optimized TOPFlash...
- Zhang J, Li Y, Liu Q, Lu W, Bu G. Wnt signaling activation and mammary gland hyperplasia in MMTV-LRP6 transgenic mice: implication for breast cancer tumorigenesis. Oncogene. 2010;29:539-49 pubmed publisher..We found that the expression of Wnt signaling co-receptor, LRP6, is upregulated in a subset of human breast cancer tissues and cell lines...
- Keramati A, Singh R, Lin A, Faramarzi S, Ye Z, Mane S, et al. Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A. 2011;108:1914-8 pubmed publisher..We previously identified a mutation in LDL receptor-related protein 6 (LRP6), LRP6(R611C), that causes early atherosclerosis...
- Berwick D, Harvey K. The importance of Wnt signalling for neurodegeneration in Parkinson's disease. Biochem Soc Trans. 2012;40:1123-8 pubmed..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression. ..
- Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407:530-5 pubmed..to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction...
- Pan W, Choi S, Wang H, Qin Y, Volpicelli Daley L, Swan L, et al. Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science. 2008;321:1350-3 pubmed publisher..by inducing phosphorylation of one of the Wnt receptors, low-density lipoprotein receptor-related protein 6 (LRP6), at threonine residue 1479 (Thr1479) and serine residue 1490 (Ser1490)...
- Sakane H, Yamamoto H, Michiue T, Kikuchi A. Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell. 2008;15:37-48 pubmed publisher..in parallel to induce the caveolin-dependent internalization of low-density-lipoprotein receptor-related protein 6 (LRP6), as well as the phosphorylation of LRP6 and the recruitment of Axin to LRP6 on the cell surface membrane...
- Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-5 pubmed..LDL-receptor-related protein 6 (LRP6) is required during Wnt/beta-catenin signalling in Drosophila, Xenopus and mouse, possibly acting as a co-receptor ..
- Wolf J, Palmby T, Gavard J, Williams B, Gutkind J. Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6. FEBS Lett. 2008;582:255-61 pubmed..By the use of full-length LRP6 mutants harboring multiple mutations involving the five PPPS/TP motifs, we found that this first PPPS/TP ..
- Tezuka N, Brown A, Yanagawa S. GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway. Biochem Biophys Res Commun. 2007;356:648-54 pubmedLow-density lipoprotein receptor-related protein 6 (LRP6) is a component of cell-surface receptors for Wnt proteins and Wnt is known to promote recruitment of Axin by LRP6 thereby inhibiting beta-catenin's degradation...
- Liu G, Bafico A, Harris V, Aaronson S. A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor. Mol Cell Biol. 2003;23:5825-35 pubmedLDL receptor-related protein 6 (LRP6) is a Wnt coreceptor in the canonical signaling pathway, which plays essential roles in embryonic development...
- Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770-5 pubmed..in Xenopus embryos and mammalian cells by binding to the extracellular domain of the Wnt coreceptors LRP5 and LRP6 and disrupting Wnt-induced Frizzled-LRP complex formation...
- Mi K, Johnson G. Regulated proteolytic processing of LRP6 results in release of its intracellular domain. J Neurochem. 2007;101:517-29 pubmedLow-density lipoprotein receptor-related protein 6 (LRP6) is a member of low-density lipoprotein receptor (LDLR) family which cooperates with Frizzled receptors to transduce the canonical Wnt signal...
- Li Y, Chen J, Lu W, McCormick L, Wang J, Bu G. Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding. J Cell Sci. 2005;118:5305-14 pubmedWnt co-receptors LRP5 and LRP6 are two members of the low-density lipoprotein receptor family...
- Wei W, Lu Q, Chaudry G, Leppla S, Cohen S. The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin. Cell. 2006;124:1141-54 pubmed..Here we show that low density lipoprotein receptor-related protein 6 (LRP6), previously known to be a coreceptor for the Wnt signaling pathway, is required for anthrax toxin lethality in ..
- Liu W, Mani S, Davis N, Sarrafzadegan N, Kavathas P, Mani A. Mutation in EGFP domain of LDL receptor-related protein 6 impairs cellular LDL clearance. Circ Res. 2008;103:1280-8 pubmed publisherMutation in the EGFP domain of LDL receptor-related protein 6 (LRP6(R611C)) is associated with hypercholesterolemia and early-onset atherosclerosis, but the mechanism by which it causes disease is not known...
- Brown S, Twells R, Hey P, Cox R, Levy E, Soderman A, et al. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun. 1998;248:879-88 pubmed..This gene, termed LDL receptor-related protein 6 (LRP6), encodes a transmembrane protein which has 71% identity and is structurally similar to the protein encoded by LRP5,..
- Bafico A, Liu G, Yaniv A, Gazit A, Aaronson S. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol. 2001;3:683-6 pubmed..is mediated by the Fz receptor and a recently identified low-density-lipoprotein-receptor-related co-receptor, LRP6/Arrow...
- Ahn V, Chu M, Choi H, Tran D, Abo A, Weis W. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell. 2011;21:862-73 pubmed publisher..The LRP5/6 ectodomain contains four β-propeller/EGF-like domain repeats. The first two repeats, LRP6(1-2), bind to several Wnt variants, whereas LRP6(3-4) binds other Wnts...
- Chen S, Bubeck D, MacDonald B, Liang W, Mao J, Malinauskas T, et al. Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling. Dev Cell. 2011;21:848-61 pubmed publisherLDL-receptor-related protein 6 (LRP6), alongside Frizzled receptors, transduces Wnt signaling across the plasma membrane...
- Hsieh J, Lee L, Zhang L, Wefer S, Brown K, DeRossi C, et al. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell. 2003;112:355-67 pubmed..MESD functions in the endoplasmic reticulum as a specific chaperone for LRP5 and LRP6, which in conjunction with Frizzled, are coreceptors for canonical WNT signal transduction...
- George A, Leahy H, Zhou J, Morin P. The vacuolar-ATPase inhibitor bafilomycin and mutant VPS35 inhibit canonical Wnt signaling. Neurobiol Dis. 2007;26:125-33 pubmed..we performed a GST fusion protein pulldown experiment and identified a possible indirect interaction between the LRP6 intracellular domain and vacuolar protein sorting protein 35 (VPS35)...
- Bourhis E, Tam C, Franke Y, Bazan J, Ernst J, Hwang J, et al. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010;285:9172-9 pubmed publisher..this report we describe insect cell expression and purification of soluble mouse Fz8 cysteine-rich domain and human LRP6 extracellular domain and show that they inhibit Wnt/beta-catenin signaling in cellular assays...
- Sakane H, Yamamoto H, Kikuchi A. LRP6 is internalized by Dkk1 to suppress its phosphorylation in the lipid raft and is recycled for reuse. J Cell Sci. 2010;123:360-8 pubmed publisher..The phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), a single-span transmembrane Wnt receptor, plays a vital role in this signaling...
- Sato A, Yamamoto H, Sakane H, Koyama H, Kikuchi A. Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 2010;29:41-54 pubmed publisher..As another action of Wnt5a, it inhibited Wnt3a-dependent lipoprotein receptor-related protein 6 (LRP6) phosphorylation and beta-catenin accumulation...
- Guidato S, Itasaki N. Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6. Dev Biol. 2007;310:250-63 pubmed..Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the ..
- Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, et al. Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development. 2008;135:367-75 pubmed..and is initiated by the action of the frizzled (Fz) receptor, its coreceptor LDL receptor-related protein 6 (Lrp6), and the cytoplasmic dishevelled (Dvl) protein...
- Beagle B, Mi K, Johnson G. Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity. J Cell Biochem. 2009;108:886-95 pubmed publisher..b>LRP6 is an essential co-receptor for Wnt/beta-catenin signaling; as transduction of the Wnt signal is strongly dependent ..
- MacDonald B, Yokota C, Tamai K, Zeng X, He X. Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6. J Biol Chem. 2008;283:16115-23 pubmed publisherLow density lipoprotein receptor-related protein 6 (LRP6) and its homologue LRP5 serve as Wnt co-receptors that are essential for the Wnt/beta-catenin pathway...
- Wang K, Zhang Y, Li X, Chen L, Wang H, Wu J, et al. Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem. 2008;283:23371-5 pubmed publisher..Dkk1 residues Arg(197), Ser(198), and Lys(232) are specifically involved in its binding to Kremen rather than to LRP6. These residues are localized at a surface that is at the opposite side of the LRP6-binding surface based on a ..
- Piao S, Lee S, Kim H, Yum S, Stamos J, Xu Y, et al. Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS ONE. 2008;3:e4046 pubmed publisher..Binding of Wnts to the coreceptors Frizzled and LRP6/5 leads to phosphorylation of PPPSPxS motifs in the LRP6/5 intracellular region and the inhibition of GSK3beta ..
- Liu C, Prior J, Piwnica Worms D, Bu G. LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy. Proc Natl Acad Sci U S A. 2010;107:5136-41 pubmed publisher..Here, we show that expression of the Wnt signaling coreceptor LRP6 is up-regulated in a subpopulation of human breast cancers...
- Berwick D, Harvey K. LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6. Hum Mol Genet. 2012;21:4966-79 pubmed publisher..Wnt stimulation, where it binds to the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) in cellular models. LRRK2, therefore, bridges membrane and cytosolic components of Wnt signaling...
- Du C, Lv Z, Cao L, Ding C, Gyabaah O, Xie H, et al. MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6 and PIK3R2. J Transl Med. 2014;12:259 pubmed publisher..b>LRP6 and PIK3R2 were identified as targets of miR-126-3p...
- Ren D, Chen J, Li Z, Yan H, Yin Y, Wo D, et al. LRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis. Nat Commun. 2015;6:6906 pubmed publisher..Here we report that Wnt receptor Frizzled (Frz) and theco-receptors LRP5 and LRP6 (LRP5/6) directly interact with each other and this interaction is regulated by the LRP6 ectodomain...
- Wen Q, Zhao J, Bai L, Wang T, Zhang H, Ma Q. miR-126 inhibits papillary thyroid carcinoma growth by targeting LRP6. Oncol Rep. 2015;34:2202-10 pubmed publisher..Furthermore, low-density lipoprotein receptor‑related protein 6 (LRP6), a regulator of the Wnt/β‑catenin signaling cascade, was identified as a crucial target gene of miR-126...
- Xia S, Ji R, Zhan W. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/?-catenin signaling pathway. BMC Neurol. 2017;17:30 pubmed publisher..The study also demonstrated that LRP6, as a receptor of the Wnt/?-catenin pathway, was a target of lncRNA PTCSC3...