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Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway
Open accessAbstract
To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.
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“The canonical Wnt signalling pathway is mainly involved in cell proliferation and survival in vital biological processes, including organogenesis and embryogenesis.1,2”
From Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function (2024) · cites this paper as [1]
In the citing paper
“The binding of Wnt to the Fz/LRP5/6 complex induces the membrane translocation of a key negative regulator of signaling Axin, which binds to a conserved sequence in the cytoplasmic tail of LRP5/6.27,28”
From Wnt signal transduction pathways (2008) · cites this paper as [27]
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“Wnt ligands are thought to bind to and signal through members of the Frizzled family of seven transmembrane domain receptors and the low-density lipoprotein receptor-related proteins LRP5 and LRP6, which function as Wnt coreceptors (3, 28 , 37, 46, 47).”
BackgroundYou Wnt some, you lose some: oncogenes in the Wnt signaling pathway
van Es, J. H., Barker, N., & Clevers, H. C. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00012-6 · Cited by 238
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BackgroundInfluentialSelf-citationWnt Stabilization of β-Catenin Reveals Principles for Morphogen Receptor-Scaffold Assemblies
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Osteogenic Differentiation of Periosteal Cells During Fracture Healing
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“…phosphorylating b catenin in the cytoplasm, enablingb-catenin to translocate to the nucleuswhere it interacts with members of the T-cell factor/ lymphocyte enhancer factor (TCF/LEF) family to activate Wnt target genes (Mao et al., 2001; Clevers, 2006; Silkstone et al., 2008; Kim et al., 2013) (Fig.”
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“…of the family of seven transmembrane domain receptors known as Frizzleds, and the co-receptor lipoprotein-receptor-related proteins 5 or 6 (LRP5/6) [Yang-Snyder et al., 1996; He et al., 1997; Slusarski et al., 1997; Wang et al., 1997; Hsieh et al., 1999a; Pinson et al., 2000; Mao et al., 2001a,b].”
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Gao, C., Wang, Y., Broaddus, R. R., Sun, L., Xue, F., & Zhang, W. (2017) · Oncotarget · doi:10.18632/oncotarget.23695 · Cited by 227
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“It is a concentration-limiting protein [25], and its cellular level is stabilized by SUMOylation [26] and decreased by degradation involving activated low-density lipoprotein receptor related protein 5/6 (LRP5/6) [27] and tankyrases [28].”
BackgroundLRP5 Mutations Linked to High Bone Mass Diseases Cause Reduced LRP5 Binding and Inhibition by SOST
Semënov, M. V., & He, X. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609509200 · Cited by 221
Lipoprotein receptor signalling in atherosclerosis
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The low-density lipoprotein receptor gene family: a cellular Swiss army knife?
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“Phosphorylated LRP6 has a high affinity for Axin and promotes further recruitment of cytoplasmic Axin-bound GSK3 complexes to the cell surface (Mao et al. 2001; Zeng et al. 2008).”
BackgroundResultInfluentialNon-canonical Wnt signalling and regulation of gastrulation movements
Tada, M., Concha, M. L., & Heisenberg, C. (2002) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084-9521(02)00052-6 · Cited by 211
Regulation of Wnt signaling by protein-protein interaction and post-translational modifications
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“Wnt causes the translocation of Axin to the membrane and enhances the interaction between Axin and LRP5/6 (Mao et al., 2001; Tamai et al., 2004).”
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“However, we find that intracellular region of LRP6 directly binds to GSK3b through the Ser/Thr rich cluster and thereby mediates the recruitment of Axin, suggesting PLoS ONE | www.plosone.org 6 December 2008 | Volume 3 | Issue 12 | e4046 that b-catenin associates indirectly with LRP6 through GSK3b and Axin.”
BackgroundInfluentialLRP5 and Wnt Signaling: A Union Made for Bone
Johnson, M. L., Harnish, K., Nusse, R., & Hul, W. V. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040816 · Cited by 211
“While genetic evidence has implicated LRP6 in Wnt signaling, analysis of different mammalian cell lines indicates that LRP5 is also involved in the canonical Wnt signal transduction pathway.((1,50)) Other cell culture experiments using a Lef/TCF-dependent Luciferase assay show that Arrow/LRP5/6 functions cooperatively…”
Wnt signaling promotes oncogenic transformation by inhibiting c-Myc–induced apoptosis
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“To confirm our results from Wnt-expressing RIE cells, we also applied a paracrine coculture assay to demonstrate that Wnt antiapoptotic activity can be conferred in a paracrine fashion (Jue et al., 1992; Mao et al., 2001a,b).”
BackgroundAutosomal Recessive Familial Exudative Vitreoretinopathy Is Associated with Mutations in LRP5
Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., & Hejtmancik, J. F. (2004) · The American Journal of Human Genetics · doi:10.1086/425080 · Cited by 207
“This binding is facilitated by Wnt and is a part of Wnt signaling (Mao et al. 2001).”
BackgroundT‐cell factors: turn‐ons and turn‐offs
Hurlstone, A. F. L., & Clevers, H. C. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2303 · Cited by 208
Cselenyi, C. S., Jernigan, K. K., Tahinci, E., Thorne, C. A., Lee, L. A., & Lee, E. N. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803025105 · Cited by 207
“LRP5 overexpression was initially shown to promote Axin degradation in cultured mammalian cells (6).”
BackgroundMethodInfluentialWnt Signaling Pathway in Mammary Gland Development and Carcinogenesis
Turashvili, G., Bouchal, J., Burkadze, G., & Kolář, Z. (2006) · Pathobiology · doi:10.1159/000098207 · Cited by 210
“In addition, another member of the Wnt gene family, Wnt10b (formerly Wnt12), is expressed in the mammary buds at this time. It was initially suggested that Wnt10b regulates canonical Wnt signaling in mammary bud development, acting on either the epithelial component, the mesenchymal component, or both [”
BackgroundThe WNT signalling pathway and diabetes mellitus
Jin, T. (2008) · Diabetologia · doi:10.1007/s00125-008-1084-y · Cited by 211
“They induced TCF/LEF-mediated transcription and stabilised β-cat [ 41 ].”
BackgroundInfluentialBone remodelling: its local regulation and the emergence of bone fragility
Martin, T. J., & Seeman, E. (2008) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2008.07.006 · Cited by 211
Structural Basis of Wnt Signaling Inhibition by Dickkopf Binding to LRP5/6
Ahn, V. E., Chu, M. L.-H., Choi, H., Tran, D. P., Abo, A., & Weis, W. I. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.09.003 · Cited by 204
“LRP5/6 repeat 3, which binds to Dkk1_C, is needed for Dkk1 binding and Wnt1 antagonism (Mao et al., 2001a; Zhang et al., 2004), yet Wnt1 and many other Wnt variants appear to bind the LRP5/6(1-2) region (Gong et al., 2010).”
BackgroundInfluentialThe role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway
Chen, H.-J., Lin, C.-M., Lin, C.-S., Perez-Olle, R., Leung, C. L., & Liem, R. K. H. (2006) · Genes & Development · doi:10.1101/gad.1411206 · Cited by 191
“Upon Wnt stimulation, Axin is translocated from the cytoplasm to the cell membrane, where it binds to LRP5 and is subsequently degraded (Mao et al. 2001).”
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Liu, X., Rubin, J. S., & Kimmel, A. R. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.050 · Cited by 198
Wnt Signaling and the Control of Human Stem Cell Fate
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The Role of Ryk and Ror Receptor Tyrosine Kinases in Wnt Signal TransductionPreprint
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“The mammalian genome encodes 19 different Wnts, which can mediate their signaling effects through 10 different FZDs that act in concert with the LRP5 and LRP6 coreceptors.”
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Behrens, J., & Lustig, B. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.041815jb · Cited by 200
Wnt/Beta-Catenin Signaling Regulation and a Role for Biomolecular Condensates
Schaefer, K. N., & Peifer, M. A. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.01.025 · Cited by 195
“One common consequence of long-term Wnt signaling is down-regulation of Axin protein levels (Kofron et al., 2007; Liu et al., 2005; Mao et al., 2001; Tolwinski et al., 2003; Yang et al., 2016).”
BackgroundRegulation of Lrp6 phosphorylation
Niehrs, C., & Shen, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0329-3 · Cited by 195
“Axin binding to Lrp6 is very likely direct, since truncated Axin interacts with the Lrp6 cytoplasmic domain in yeast two-hybrid assays [ 41 , 118].”
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“These additional factors include the LRP5/6 coreceptors, which are required for most aspects of canonical Wnt signaling (24, 33, 38).”
BackgroundMEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer
Zhan, T., Ambrosi, G., Wandmacher, A. M., Rauscher, B., Betge, J., Rindtorff, N., Häussler, R. S., Hinsenkamp, I., Bamberg, L., Hessling, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09898-0 · Cited by 189
Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin
Cong, F., & VARMUS, H. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307344101 · Cited by 189
Li, J., & Wang, C. (2008) · Nature Cell Biology · doi:10.1038/ncb1684 · Cited by 195
“1a , overexpression of TBL1 significantly enhanced β-cat M -stimulated transcription, as determined by a SuperTopflash reporter assay that specifically measured β-catenin–Tcf-mediated transcriptional activitie”
MethodVijay, N., Bossu, C. M., Poelstra, J. W., Weissensteiner, M. H., Suh, A., Kryukov, A. P., & Wolf, J. B. W. (2016) · Nature Communications · doi:10.1038/ncomms13195 · Cited by 192
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“Wnt proteins relate to cell surfaces and extracellular matrix and bind to members of the Frizzled family of G protein–coupled receptors (3, 4).”
BackgroundMechanistic Insights Into Diabetes Mellitus and Oxidative Stress
Maiese, K., Chong, Z. Z., & Shang, Y. C. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707781058968 · Cited by 186
Emerging links between CDK cell cycle regulators and Wnt signaling
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“Moreover, truncated forms of LRP5 or -6 lacking the extracellular domain can act as constitutively active signaling molecules, activating the -catenin pathway in a ligand-independent and Frizzled-independent manner (11, 49, 50, 84).”
BackgroundInfluentialInhibition of GSK3 by Wnt signalling – two contrasting models
Metcalfe, C., & Bienz, M. (2011) · Journal of Cell Science · doi:10.1242/jcs.091991 · Cited by 181
“It has been proposed that the phosphorylated PPPSPxS motifs constitute a docking site for Axin (Mao et al., 2001), thereby promoting a crucial protein interaction for the functioning of the signalosome, possibly by synergising with the DIX-dependent Dishevelled–Axin interaction, in order to stabilise and sustain the s…”
BackgroundInfluentialKulkarni, N. H., Onyia, J. E., Zeng, Q., Tian, X. Y., Liu, M., Halladay, D., Frolik, C. A., Engler, T. A., Wei, T., Kriauciunas, A., et al. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060316 · Cited by 180
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LRP2/megalin is required for patterning of the ventral telencephalon
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“Sonic hedgehog activity defines the ventral neural tube and establishes ventral neuronal and oligodendroglial cell populations (Marin and Rubenstein, 2001; Nery et al., 2001; Rowitch et al., 1999; Lu et al., 2000).”
BackgroundJia, J., Tong, C., & Jiang, J. (2003) · Genes & Development · doi:10.1101/gad.1136603 · Cited by 178
“Physical association of the receptor complex with a downstream signaling component has also been demonstrated for the canonic Wnt pathway whereby the Wnt coreceptor LRP-5 interacts with Axin, a molecular scaffold in the Wnt pathway (Mao et al. 2001).”
BackgroundBaarsma, H. A., Königshoff, M., & Gosens, R. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.002 · Cited by 179
“DKK-2 may be an exception as this specific DKK may have a stimulatory or inhibitory effect on canonical WNT signaling depending on cellular context (Ahn et al., 2011; Brott & Sokol, 2002; B. Mao et al., 2001; M. AC C EP TE D M AN U SC R IP T V. Semenov et al., 2001; W. Wu et al., 2000).”
BackgroundControlling mesenchymal stem cell differentiation by TGFβ family members
Roelen, B. A. J., & ten Dijke, P. (2003) · Journal of Orthopaedic Science · doi:10.1007/s00776-003-0702-2 · Cited by 178
LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence
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The Wnt signaling pathway: Aging gracefully as a protectionist?
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“Wnt signaling also can be transmitted through the binding of extracellular domain of LRP-5/6 to Axin, a key component in the GSK-3β complex, indicating that the LRP-5/6 receptor is an important part of the Wnt-FZD signaling pathway (Mao et al., 2001; Tolwinski et al., 2003).”
BackgroundInfluentialWnt signalling and the mechanistic basis of tumour development
Ilyas, M. (2005) · The Journal of Pathology · doi:10.1002/path.1692 · Cited by 171
“Analysis of the location of APC mutations shows that there is a very well-defined 3′ boundary in the APC gene which is at the site of the Axin binding region of APC [107,108].”
BackgroundInfluentialKokubu, C., Heinzmann, U., Kokubu, T., Sakai, N., Kubota, T., Kawai, M., Wahl, M. B., Galcerán, J., Grosschedl, R., Ozono, K., et al. (2004) · Development · doi:10.1242/dev.01405 · Cited by 169
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Self-citationThe role of the Wnt signaling pathway in osteoblast commitment and differentiation
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The LRP5 High-Bone-Mass G171V Mutation Disrupts LRP5 Interaction with Mesd
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“Furthermore, LRP5 and Arrow were found to be involved in transducing the canonical Wnt signals by binding Axin and leading to Axin degradation and -catenin stabilization ( 24 , 35).”
BackgroundSelf-citationPathology and pathogenesis of craniopharyngiomas
Larkin, S. J., & Ansorge, O. (2012) · Pituitary · doi:10.1007/s11102-012-0418-4 · Cited by 162
“Binding of Wnt promotes dimerization of Fz with LRP5/6 in order to initiate Wnt signaling [19].”
Regulation of Wnt/β‐catenin signaling by protein kinases
Verheyen, E. M., & Gottardi, C. J. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22019 · Cited by 165
Chen, Y., Hu, Y., Zhou, T., Zhou, K. K., Mott, R., Wu, M., Boulton, M. E., Lyons, T. J., Gao, G., & Ma, J. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080945 · Cited by 159
Mechanistic insights into Wnt–β-catenin pathway activation and signal transduction
Maurice, M. M., & Angers, S. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00823-y · Cited by 180
“CK1α is an obligatory component of the β-catenin destruction complex that is recruited to the plasma membrane by Wnt-stimulated receptors 193,194 .”
Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake
Chung, N., & Wasan, K. M. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.12.003 · Cited by 165
Hsieh, M., Johnson, M., Greenberg, N. M., & Richards, J. S. (2002) · Endocrinology · doi:10.1210/en.143.3.898 · Cited by 156
A Form of the Metabolic Syndrome Associated with Mutations in DYRK1B
Keramati, A. R., Fathzadeh, M., Go, G., Singh, R., Choi, M., Faramarzi, S., Mane, S., Kasaei, M. M., Sarajzadeh, K., Hwa, J., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1301824 · Cited by 161
Saraswati, S., Alfaro, M. P., Thorne, C. A., Atkinson, J. B., Lee, E. N., & Young, P. P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015521 · Cited by 154
“This interaction recruits axin2 and disheveled to the LRP protein and frizzled receptor, respectively [12,13,14], and further inhibits the kinase activity of the b-catenin destruction complex [15].”
BackgroundAxin: A Master Scaffold for Multiple Signaling Pathways
Luo, W., & Lin, S. (2004) · Neurosignals · doi:10.1159/000076563 · Cited by 154
The role of the Wnt signalling pathway in colorectal tumorigenesis
Behrens, J. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330672 · Cited by 160
Winding through the WNT pathway during cellular development and demise.
Li, F., Chong, Z. Z., & Maiese, K. (2006) · PubMed · doi:10.14670/hh-21.103 · Cited by 154
Tolwinski, N. S., & Wieschaus, E. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.02.003 · Cited by 151
“13 Mao, J. et al. (2001) Low-density lipoprotein receptor-related protein-5”
Wei, W., Li, M., Wang, J., Nie, F., & Li, L. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00251-12 · Cited by 152
“Wnt3a-CM and Ctrl-CM were described previously (24).”
Self-citationLrp5 and Lrp6 redundantly control skeletal development in the mouse embryo
Joeng, K. S., Schumacher, C. A., Diegel, C. R., Long, F., & Williams, B. O. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.08.020 · Cited by 147
“…6, and a member of the Frizzled receptor family, to activate an intracellular signaling cascade that culminates in β-catenin-dependent transcriptional regulation; this mechanism is commonly known as the canonical pathway (Huelsken and Birchmeier, 2001; Mao et al., 2001; Pinson © 2011 Elsevier Inc.”
BackgroundWnt/β-catenin Signaling in Embryonic Stem Cell Self-renewal and Somatic Cell Reprogramming
Miki, T., Yasuda, S.-Y., & Kahn, M. (2011) · Stem Cell Reviews and Reports · doi:10.1007/s12015-011-9275-1 · Cited by 149
“Upon binding of Wnt to its receptor Fz and its co-receptors LRP5/6, Dvl recruits Axin to the receptor complex [21].”
BackgroundWnt signaling in breast cancer: have we come full circle?
Brown, A. M. C. (2001) · Breast Cancer Research · doi:10.1186/bcr321 · Cited by 147
“Wnt receptors themselves could be candidate oncogenes in this context, and mutated forms of LRP5 and LRP6 have recently been shown to be capable of constitutive Wnt/β-catenin signaling in cell culture [22,23].”
BackgroundDejmek, J. S., Säfholm, A., Nielsen, C. K., Andersson, T., & Leandersson, K. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02354-05 · Cited by 145
Haÿ, E., Laplantine, E., Geoffroy, V., Frain, M., Kohler, T., Müller, R., & Marie, P. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00349-08 · Cited by 147
“AxinLRP5 interaction induced by Wnt results in axin destabilization that contributes to -catenin stabilization and LEF-1 transcription (38, 50).”
BackgroundInfluentialNuclear Targeting by the Growth Factor Midkine
Shibata, Y., Muramatsu, T., Hirai, M., Inui, T., Kimura, T., Saito, H., McCormick, L. M., Bu, G., & Kadomatsu, K. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.19.6788-6796.2002 · Cited by 147
“differentiation, and carcinogenesis (45, 56, 69, 74).”
Regulation of Wnt/β‐catenin signalling by tankyrase‐dependent poly(ADP‐ribosyl)ation and scaffolding
Mariotti, L., Pollock, K., & Guettler, S. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14038 · Cited by 144
“While the intact LRP5 C-terminus is required for AXIN binding (Mao et al., 2001), it is presently not clear whether AXIN and LRP5/6 interact directly (Mao et al., 2001; Kim et al., 2013; Wang et al., 2013), but there are indications that this may be the case (MacDonald et al., 2011).”
Khan, N. I., Bradstock, K. F., & Bendall, L. J. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06667.x · Cited by 146
“Canonical activation usually involves Wnt proteins binding to two receptor molecules, Frizzled (Fzd), which belong to a class of seven-pass transmembrane receptors, and lipoprotein receptor-related proteins 5 or 6 (LRP5/6) (Tamai et al, 2000; Mao et al, 2001).”
BackgroundOsteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies
Hamerman, D. (2005) · QJM · doi:10.1093/qjmed/hci077 · Cited by 146
Casein Kinase Iε Modulates the Signaling Specificities of Dishevelled
Cong, F., Schweizer, L., & VARMUS, H. E. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.5.2000-2011.2004 · Cited by 143
“The kinase assays were initiated by the addition of 2 g of GST-Jun(1-109) substrate protein, and 10 Ci of [ -32P]ATP in a volume of 25 l.”
BackgroundMethodLDL receptor relatives at the crossroad of endocytosis and signaling
Schneider, W. J., & Nimpf, J. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-2183-z · Cited by 142
The Role of Grp 78 in α2-Macroglobulin-induced Signal Transduction
Misra, U. K., Gonzalez–Gronow, M., Gawdi, G., Hart, J. P., Johnson, C. E., & Pizzo, S. V. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206174200 · Cited by 141
Similarities between the Hedgehog and Wnt signaling pathways
Kalderon, D. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)02388-7 · Cited by 141
“As the presence of Wnt enables binding of Fz to LRP5/6 [ 14 ], apposition of the two receptors might be key to initiating signal transduction.”
BackgroundThe Ubiquitin-Specific Protease USP34 Regulates Axin Stability and Wnt/β-Catenin Signaling
Lui, T. T. H., Lacroix, C., Ahmed, S. M., Goldenberg, S. J., Leach, C. A., Daulat, A. M., & Angers, S. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01094-10 · Cited by 144
“site for axin (36, 53) that is suspected to inactivate the destruc-”
BackgroundAdamska, M., Larroux, C., Adamski, M., Green, K., Lovas, E., Koop, D., Richards, G. S., Zwafink, C., & Degnan, B. M. (2010) · Evolution & Development · doi:10.1111/j.1525-142x.2010.00435.x · Cited by 139
Korswagen, H. C. (2002) · BioEssays · doi:10.1002/bies.10145 · Cited by 135
Molecular causes of colon cancer
Oving, I. M., & Clevers, H. C. (2002) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2002.01004.x · Cited by 135
A Novel Mechanism for Wnt Activation of Canonical Signaling through the LRP6 Receptor
Liu, G., Bafico, A., Harris, V., & Aaronson, S. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5825-5835.2003 · Cited by 136
“Our findings as well as those of others (28) indicate that the NH2-terminally truncated LRP mutants lacking the extracellular domain are capable of canonical signaling independent of either a Wnt ligand or frizzled receptor.”
BackgroundResultInfluentialMaupin, K. A., Droscha, C. J., & Williams, B. O. (2013) · Bone Research · doi:10.4248/br201301004 · Cited by 133
Molecular Bases of the Regulation of Bone Remodeling by the Canonical Wnt Signaling Pathway
Glass, D. A., & Karsenty, G. (2006) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(05)73002-7 · Cited by 138
A role for Wnt/β-catenin signaling in lens epithelial differentiation
Stump, R. J. W., Ang, S., Chen, Y., von Bahr, T., Lovicu, F. J., Pinson, K. I., de Iongh, R. U., Yamaguchi, T. P., Sassoon, D. A., & McAvoy, J. W. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00179-9 · Cited by 134
“Recent studies indicate that LRP5/6, when part of the Wnt ligand-receptor complex, removes axin from the -catenin destruction complex, resulting in stabilization of -catenin and its translocation to the nucleus (Mao et al., 2001; Zorn, 2001).”
BackgroundProtein phosphatase 1 regulates assembly and function of the β‐catenin degradation complex
Luo, W., Peterson, A. G., Garcia, B. A., Coombs, G. S., Kofahl, B., Heinrich, R., Shabanowitz, J., Hunt, D. F., Yost, H. J., & Virshup, D. M. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601607 · Cited by 132
“After specific Wnt molecules bind to membrane receptors of the Fz and LRP5/6 families, a signal- ing cascade is initiated that results in specific phosphory- lation of the LRP5/6 cytoplasmic domain (Mao et al, 2001; Tamai et al, 2004; Davidson et al, 2005; Zeng et al, 2005).”
BackgroundFrizzled receptor dimerization is sufficient to activate the Wnt/β-catenin pathway
Carron, C., Pascal, A., Djiane, A., Boucaut, J., Shi, D., & Umbhauer, M. (2003) · Journal of Cell Science · doi:10.1242/jcs.00451 · Cited by 129
“…frizzled receptor, the Axin–GSK3–APC–β-catenin complex is disrupted by a process involving the cytoplasmic protein Dishevelled (Dsh), and dephosphorylation and recruitment of Axin to LRP5, which is associated with Axin destabilization (Mao et al., 2001; Smalley et al., 1999; Yamamoto et al., 1999).”
BackgroundThe Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegansPreprint
Korswagen, H. C., Coudreuse, D., Betist, M. C., van de Water, S., Zivkovic, D., & Jc, C. (2002) · Genes & Development · doi:10.1101/gad.981802 · Cited by 137
“In response to the MOM-2/Wnt pathway and a parallel mitogen-activated protein kinase (MAPK) pathway consisting of MOM-4/TAK1 and LIT1/NLK, POP-1 levels are down-regulated in E (Meneghini et al. 1999; Rocheleau et al. 1999).”
Regulation of leukemic cell adhesion, proliferation, and survival by β-catenin
Chung, E. J., Hwang, S., Nguyen, P., Lee, S., Kim, J.-S., Kim, J. W., Henkart, P. A., Bottaro, D. P., Soon, L., Bonvini, P., et al. (2002) · Blood · doi:10.1182/blood.v100.3.982 · Cited by 131
Metadata
- Authors
- Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., & Wu, D.
- Affiliations
- University of Connecticut (US)
- Chinese Academy of Sciences (CN)
- University of Washington (US)
- University of Rochester Medicine (US)
- Setsunan University (JP)
- Corresponding author
- Wu, Dianqing
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 7
- Issue
- 4
- Pages
- 801-809
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2152769008
- Cited by
- 839
- References
- 32
- Citations by year
- 2026: 1 · 2025: 15 · 2024: 20 · 2023: 23 · 2022: 25 · 2021: 21 · 2020: 25 · 2019: 25 · 2018: 25 · 2017: 27 · 2016: 23 · 2015: 30 · 2014: 37 · 2013: 46 · 2012: 40
- FWCI
- 17.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29gm053162-04)
- National Cancer Institute (R01CA085420, CA85420)
- National Institute of General Medical Sciences (GM53162, GM54167)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD027262, HD27262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- low-density lipoprotein receptor-related protein 5, Axin, Wnt/β-catenin signaling, β-catenin stabilization, protein-protein interaction
- MeSH terms
- Amino Acid Sequence, Animals, Mammals, Molecular Sequence Data, Protein Binding, Proteins, Proto-Oncogene Proteins, Receptors, LDL, Repressor Proteins, Signal Transduction, Gene Expression, Mutagenesis, 3T3 Cells, Protein Structure, Tertiary, Calcium-Calmodulin-Dependent Protein Kinases, COS Cells, LDL-Receptor Related Proteins, Zebrafish Proteins, Glycogen Synthase Kinase 3, Wnt Proteins, Mice, Axin Protein, Low Density Lipoprotein Receptor-Related Protein-5
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