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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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Cites
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Cited by
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Items 301–400 of 839
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“5A); these mutants have been previously reported to be desensitized to the canonical WNT signals (14, 15).”
BackgroundSelf-citationControl of osteogenesis by the canonical Wnt and BMP pathways in vivo
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“related proteins LRP-5/6 [93, 94].”
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“As a consequence of LRP5/6 phosphorylation, Axin and GSK3 are recruited to the complex (Mao et al., 2001; Zeng et al., 2005).”
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Axin Utilizes Distinct Regions for Competitive MEKK1 and MEKK4 Binding and JNK Activation
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PR72, a novel regulator of Wnt signaling required for Naked cuticle functionPreprint
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HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance
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“With active signal, restraining Axin by LRP5/6 prohibits formation of β-catenin destruction complex and causes an accumulation of β-catenin in the cytoplasm and its eventual translocation into the nucleus [227,231].”
BackgroundDisruption of LRP6 in osteoblasts blunts the bone anabolic activity of PTH
Li, C., Xing, Q., Yu, B., Xie, H., Wang, W., Shi, C., Crane, J. L., Cao, X., & Wan, M. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1962 · Cited by 79
Maiese, K. (2008) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2008.01.009 · Cited by 75
“In general, all Wnt signaling pathways are initiated by interaction of Wnt proteins with Frizzled (FZD) receptors and the binding of the Wnt protein to the FZD transmembrane receptor in the presence of the co-receptor LRP-5/6 [154] (Figure 1).”
BackgroundWingless Signaling: A Genetic Journey from Morphogenesis to Metastasis
Bejsovec, A. (2018) · Genetics · doi:10.1534/genetics.117.300157 · Cited by 74
“The intracellular domain of LRP5was also shown to bind to Axin in mouse cells (Mao et al. 2001), providing another link between the cell surface and cytosolic components of the Wg/ Wnt pathway.”
BackgroundCrosstalk mechanisms between the WNT signaling pathway and long non-coding RNAs
Zarkou, V., Γαλάρας, Α., Giakountis, A., & Hatzis, P. (2018) · Non-coding RNA Research · doi:10.1016/j.ncrna.2018.04.001 · Cited by 72
Castañon, B. I., Stapp, A. D., Gifford, C. A., SPICER, L. J., Hallford, D. M., & Gifford, J. A. H. (2012) · Journal of Animal Science · doi:10.2527/jas.2011-4696 · Cited by 73
Wei Jun, P. A. N., Pang, S., Huang, T., Guo, H., Wu, D., & Li, L. (2004) · Cell Research · doi:10.1038/sj.cr.7290232 · Cited by 72
Self-citationGoel, S., Chin, E. N., Fakhraldeen, S. A., Berry, S. M., Beebe, D. J., & Alexander, C. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.362137 · Cited by 72
Lin, Z., Gao, C., Ning, Y., He, X., Wu, W., & Chen, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804039200 · Cited by 77
A Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers
Raisch, J., Côté-Biron, A., & Rivard, N. (2019) · Cancers · doi:10.3390/cancers11081162 · Cited by 69
Interaction between LRP5 and Frat1 Mediates the Activation of the Wnt Canonical Pathway
Haÿ, E., Faucheu, C., Suc-Royer, I., Touitou, R., Stiot, V., Vayssière, B., Baron, R., Roman‐Roman, S., & Rawadi, G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411999200 · Cited by 71
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Complexity of the Wnt/β‑catenin pathway: Searching for an activation model
Tortelote, G. G., dos Reis, R. R., Mendes, F. A., & Abreu, J. G. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.08.008 · Cited by 71
Amer1/WTX couples Wnt‐induced formation of PtdIns(4,5)P2 to LRP6 phosphorylation
Tanneberger, K., Pfister, A. S., Brauburger, K., Schneikert, J., Hadjihannas, M. V., Křı́ž, V., Schulte, G., Bryja, V., & Behrens, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.28 · Cited by 70
“Notably, the previously described recruitment of Axin to the plasma membrane after Wnt stimulation was also abolished after knockdown of Amer1 (Figure 1A; Mao et al, 2001).”
BackgroundInfluentialLow density lipoprotein receptor-related protein: regulation of the plasma membrane proteome
Wu, L., Salicioni, A. M., & Gonias, S. L. (2004) · Thrombosis and Haemostasis · doi:10.1160/th04-01-0023 · Cited by 70
Dissecting Molecular Differences between Wnt Coreceptors LRP5 and LRP6
MacDonald, B. T., Semënov, M. V., Huang, H., & He, X. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023537 · Cited by 68
“Earlier findings based on yeast two-hybrid assays suggested that LRP5/6-Axin association is likely direct [30] and is mediated through phosphorylated PPPSPxS motifs as Axin-docking sites [12,13], although this model has not ruled out the caveat that GSK3-like proteins in yeast may have a role in mediating the two-hydr…”
BackgroundMethodInfluentialYellow submarine of the Wnt/Frizzled signaling: Submerging from the G protein harbor to the targets
Koval, A., Purvanov, V., Egger‐Adam, D., & Katanaev, V. L. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.005 · Cited by 70
Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway
Mi, K., & Johnson, G. V. W. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20400 · Cited by 69
“There is alsodata to suggest that Wnt may signal through LRP5/6 directly to the b-catenin destruction complex in a Fz receptor- and Dsh-independent fashion [Mao et al., 2001; Li et al., 2002].”
BackgroundResultInfluentialWnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging
Chen, D., Xie, R., Shu, B., LANDAY, A. L., Wei, C., Reiser, J., Spagnoli, A., Torquati, A., Forsyth, C. B., Keshavarzian, A., et al. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13945 · Cited by 69
Kusano, S., & Raab‐Traub, N. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.18.6393-6405.2002 · Cited by 69
“teracts with the GSK-3 binding domain of Axin without stoichiometric effects on the Axin–GSK-3 complex (20).”
BackgroundKhan, Z., Vijayakumar, S., de la Torre, T. V., Rotolo, S., & Bafico, A. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00773-07 · Cited by 73
“Evidence for LRP6-axin interaction has been provided by studies involving their cotransfection in model cells (20, 22).”
BackgroundMethodLRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation
Zhang, J., Zhang, X., Zhang, L., Zhou, F., van Dinther, M., & ten Dijke, P. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1661 · Cited by 69
“(40) Although LRP8 is in the LDLR family and shares conserved domains with LRP5/6, whether LRP8 is involved in Wnt signaling is unknown.”
BackgroundResultInfluentialLRP5/6 directly bind to Frizzled and prevent Frizzled-regulated tumour metastasis
Ren, D., Chen, J., Li, Z., Yan, H., Yin, Y., Wo, D., Zhang, J., Ao, L., Chen, B., Ito, T. K., et al. (2015) · Nature Communications · doi:10.1038/ncomms7906 · Cited by 72
Structural and Functional Characterization of the Wnt Inhibitor APC Membrane Recruitment 1 (Amer1)
Tanneberger, K., Pfister, A. S., Kriz, V., Bryja, V., Schambony, A., & Behrens, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.224881 · Cited by 62
Wnt pathway activation by ADP-ribosylation
Yang, E., Tacchelly‐Benites, O., Wang, Z., Randall, M. P., Tian, A., Benchabane, H., Freemantle, S. J., Pikielny, C. W., Tolwinski, N. S., Lee, E. N., et al. (2016) · Nature Communications · doi:10.1038/ncomms11430 · Cited by 69
Regulation of Phosphatidylinositol Kinases and Metabolism by Wnt3a and Dvl
Qin, Y., Li, L., Pan, W., & Wu, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.014399 · Cited by 70
Self-citationApigenin-induced lysosomal degradation of β-catenin in Wnt/β-catenin signaling
Lin, C.-M., Chen, H., Lin, C.-A., Wu, H., Sheu, J. J., & Chen, H. (2017) · Scientific Reports · doi:10.1038/s41598-017-00409-z · Cited by 72
Schaefer, K. N., Bonello, T., Zhang, S., Williams, C. E., Roberts, D. M., McKay, D. J., & Peifer, M. A. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007339 · Cited by 66
LDL Receptor‐Related Proteins in Neurodevelopment
May, P., & Herz, J. (2003) · Traffic · doi:10.1034/j.1600-0854.2003.00086_4_5.x · Cited by 60
“The closely related receptor LRP5 was recently shown to participate in canonical Wnt signaling by recruiting Axin upon stimulation with Wnt, thereby destabilizing the protein complex in which b-catenin is targeted for degradation (77).”
BackgroundKulkarni, N. H., Wei, T., Kumar, A., Dow, E. R., Stewart, T. R., Shou, J., N'Cho, M., Sterchi, D. L., Gitter, B. D., Higgs, R. E., et al. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21374 · Cited by 66
“…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., 1999; Pinson et al., 2000; Mao et al., 2001a,b].”
BackgroundFrizzled Receptors Activate a Novel JNK-Dependent Pathway that May Lead to Apoptosis
Lisovsky, M., Itoh, K., & Sokol, S. Y. (2002) · Current Biology · doi:10.1016/s0960-9822(01)00628-5 · Cited by 66
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The Role of Wnt Signaling In Cancer and Stem Cells
Reguart, N., He, B., Tarón, M., You, L., Jablons, D. M., & Rosell, R. (2005) · Future Oncology · doi:10.2217/14796694.1.6.787 · Cited by 66
“The canonical Wnt signaling pathway Secreted Wnt ligands bind to a transmembrane receptor complex consisting of the Fz receptors and the coreceptors LRP5 and 6 [22].”
Backgroundde Herreros, A. G., & Duñach, M. (2019) · Cells · doi:10.3390/cells8101148 · Cited by 64
“This is the diverging point of the two signaling pathways, as CK1γ phosphorylates LRP5/6 in Thr1479, creating a docking site for axin and enhancing the interactions of axin and the associated protein kinases CK1α and GSK3 with the LRP5/6 complex (Figure 1d) [22,23].”
BackgroundWNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology
Sassi, N., LAADHAR, L., Allouche, M., Achek, A., KALLEL‐SELLAMI, M., Makni, S., & Sellami, S. (2013) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2013.863919 · Cited by 64
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“Subsequently, phosphorylation of APC by CK1α and GSK3β leads to an increased AXIN -catenin APC GSK3 CK1 P P P P TRCP Proteolysis mediated by ubiquination LRP5/6 FZD DVL TCF/LEF nucleus WNT SFRPsDKK WIF SB216763 LiCl Gene target A Figure 1 The canonical Wnt/β-catenin pathway.”
InfluentialHaplotype Structure, LD Blocks, and Uneven Recombination Within the LRP5 GenePreprint
Twells, R. C. J., Mein, C. A., Phillips, M. S., Hess, J. F., Veijola, R., Gilbey, M., Bright, M., Metzker, M. L., Lie, B. A., Kingsnorth, A., et al. (2003) · Genome Research · doi:10.1101/gr.563703 · Cited by 64
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“Axin1 plays crucial roles in both the destruction of the β-catenin complex and activation of the LRP6 signaling complex [110].”
BackgroundQuantitative Phosphoproteome Profiling of Wnt3a-mediated Signaling Network
Tang, L.-Y., Deng, N., Wang, L., Dai, J., Wang, Z., Jiang, X.-S., Li, S., Li, L., Sheng, Q., Wu, D., et al. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700120-mcp200 · Cited by 63
“Wnt3a-containing conditioned medium was prepared as previously described (22).”
MethodSelf-citationThe role of GSK3 in metabolic pathway perturbations in cancer
Papadopoli, D. J., Pollak, M., & Topisirović, I. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119059 · Cited by 67
Li, Z. G., Yang, J., Vazquez, E. S., Rose, D., Vakar‐Lopez, F., Mathew, P. F., López, A., Logothetis, C. J., Lin, S.-H., & Navone, N. M. (2007) · Oncogene · doi:10.1038/sj.onc.1210694 · Cited by 62
“LRP5 and LRP6 share high homology (71% identical amino acids) and both interact with DKK1; however, no conclusive information is available as to how these co-receptors differ in mediating WNT canonical signaling (Westendorf et al., 2004).”
BackgroundInfluentialChen, T., Li, M., Ding, Y., Zhang, L. W., Xi, Y., Pan, W., Tao, D.-L., Wang, J.-Y., & Li, L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807753200 · Cited by 62
Self-citationWnt/β‐catenin signaling plays a key role in the development of spondyloarthritis
Xie, W., Zhou, L., Li, S., Hui, T., & Chen, D. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12968 · Cited by 63
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation
Ding, Y., Xi, Y., Chen, T., Wang, J., Tao, D.-L., Wu, Z., Li, Y., Li, C., Zeng, R., & Lin, L. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200803147 · Cited by 62
Self-citationCross-regulation of Wnt signaling and cell adhesion
Schambony, A., Kunz, M., & Gradl, D. (2004) · Differentiation · doi:10.1111/j.1432-0436.2004.07207002.x · Cited by 61
Haraguchi, K., Ohsugi, M., Abe, Y., Semba, K., Akiyama, T., & Yamamoto, T. S. (2007) · Oncogene · doi:10.1038/sj.onc.1210644 · Cited by 61
“In addition, Axin is recruited to the cytoplasmic domain of the Wnt co-receptor LRP5/6 (Mao et al., 2001; Tolwinski et al., 2003; Tamai et al., 2004).”
BackgroundConformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways
Lee, H., Shi, D., & Zheng, J. (2015) · eLife · doi:10.7554/elife.08142 · Cited by 57
“Axin binds LRP5/6 (Mao et al., 2001; Tamai et al., 2004), and the DIX domains of Dvl and Axin interact to further stabilize the complex (Schwarz-Romond et al., 2007; Fiedler et al., 2011).”
Olaisen, C., Müller, R., Nedal, A., & Otterlei, M. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.03.009 · Cited by 63
The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway
Egger‐Adam, D., & Katanaev, V. L. (2009) · Developmental Dynamics · doi:10.1002/dvdy.22060 · Cited by 61
Matrix-Producing Cells in Chronic Kidney Disease: Origin, Regulation, and Activation
Kramann, R., DiRocco, D. P., Maarouf, O. H., & Humphreys, B. D. (2013) · Current Pathobiology Reports · doi:10.1007/s40139-013-0026-7 · Cited by 65
Mohinta, S. (2007) · Frontiers in bioscience · doi:10.2741/2368 · Cited by 61
“It has been shown that LRP6/5 binds to Axin, a scaffolding protein, and localizes it to the plasma membrane followed by its degradation and thus leading to the dispersal of the beta-catenin destruction complex (33, 34).”
BackgroundEffects of Secreted Frizzled-Related Protein 3 on Osteoblasts In Vitro
Chung, Y., Baylink, D. J., Srivastava, A. K., Amaar, Y. G., Tapia, B., Kasukawa, Y., & Mohan, S. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040412 · Cited by 60
Cheng, C.-W., Smith, S. K., & Jones, D. S. (2003) · Experimental Cell Research · doi:10.1016/j.yexcr.2003.07.006 · Cited by 60
Papadopoulou, D., Bianchi, M. W., & Bourouis, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4909-4919.2004 · Cited by 60
“However, initial Wnt-induced events involve the activation of Disheveled (Dsh), its binding to Axin (42, 67), and the assistance of the Wnt coreceptor Arrow/LRP (47, 73) to modify the Arm/ -catenin degradation complex.”
BackgroundMissing Links in GSK3 Regulation
Dominguez, I. M., & Green, J. B. A. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0317 · Cited by 60
Dengler-Crish, C. M., Ball, H. C., Lin, L., Novak, K. M., & Cooper, L. N. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.03.021 · Cited by 58
Tissue-specific roles of Axin2 in the inhibition and activation of Wnt signaling in the mouse embryo
Qian, L., Mahaffey, J. P., Alcorn, H. L., & Anderson, K. V. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100328108 · Cited by 59
van Leeuwen, I. M. M., Byrne, H. M., Jensen, O. E., & King, J. R. (2007) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2007.01.019 · Cited by 59
Intra-epithelial Requirement of Canonical Wnt Signaling for Tooth Morphogenesis
Zhu, X., Zhao, P., Liu, Y., Zhang, X., Fu, J., Yu, H., Qiu, M. S., Chen, Y., Hsu, W., & Zhang, Z. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.462473 · Cited by 59
The high bone mass family--the role of Wnt/Lrp5 signaling in the regulation of bone mass.
Ml, J. (2004) · PubMed · Cited by 59
Regulation of Osteoblast Metabolism by Wnt Signaling
Moorer, M. C., & Riddle, R. C. (2018) · Endocrinology and Metabolism · doi:10.3803/enm.2018.33.3.318 · Cited by 60
Wingless/Wnt signaling in Drosophila: The pattern and the pathway
Bejsovec, A. (2013) · Molecular Reproduction and Development · doi:10.1002/mrd.22228 · Cited by 55
Keeping Wnt Signalosome in Check by Vesicular Traffic
Feng, Q., & Gao, N. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24853 · Cited by 60
“…two fundamental biochemical responses: (1) creation of a docking site for Axin scaffold protein to bind, thereby recruiting the destruction complex (Mao et al., 2001b; Tamai et al., 2004; Davidson et al., 2005; MacDonald et al., 2008); and (2) directly inactivating GSK3b kinase by accessing its…”
BackgroundSchmitz, Y., Rateitschak, K., & Olaf Wolkenhauer, A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.07.005 · Cited by 58
Wnt signaling: the good and the bad
Chen, X., Yang, J., Evans, P. M., & Liu, C. (2008) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2008.00440.x · Cited by 56
“Recruitment of Axin to the cell membrane inhibits its function, resulting in the stabilization of β-catenin [34].”
BackgroundOocyte‐derived R‐spondin2 promotes ovarian follicle development
Cheng, Y., Kawamura, K., Takae, S., Deguchi, M., Yang, Q., Kuo, C. J., & Hsueh, A. J. W. (2013) · The FASEB Journal · doi:10.1096/fj.12-223412 · Cited by 58
“Following binding to Frizzled receptors, Wnt ligands activate the canonical Wnt pathway mediated by dishevelled, glycogen synthase kinase 3 (GSK3), and -catenin, leading to transcriptional activation of T-cell factor/lymphoid enhancer factor-regulated genes (3).”
BackgroundSignalling dynamics in embryonic development
Sonnen, K. F., & Janda, C. Y. (2021) · Biochemical Journal · doi:10.1042/bcj20210043 · Cited by 58
Takada, R., Hijikata, H., Kondoh, H., & Takada, S. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2005.00889.x · Cited by 56
Self-citationTargeting Wnt/β-Catenin Pathway for Drug Therapy
Liu, C., Takada, K., & Zhu, D. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100066 · Cited by 58
Kim, M. J., Chia, I. V., & Costantini, F. D. (2008) · The FASEB Journal · doi:10.1096/fj.08-113910 · Cited by 56
“Wnt signal (10, 11, 27, 28), the ubiquitination of Axin”
BackgroundPan, W., Jia, Y., Wang, J., Tao, D.-L., Gan, X., Tsiokas, L., Jing, N., Wu, D., & Li, L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505922102 · Cited by 56
Self-citationCanonical Wnt/β-Catenin Signalling Is Essential for Optic Cup Formation
Hägglund, A., Berghard, A., & Carlsson, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081158 · Cited by 56
“Although the Lrp62/2 mice have microphthalmia with coloboma, they develop the basic structures of the eye: neural retina, RPE cell layer and the lens [32,71], which is in contrast to the b-catenin mutants presented in this work.”
BackgroundInfluentialDkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma
Igbinigie, E., Guo, F., Jiang, S., Kelley, C., & Li, J. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.11.023 · Cited by 55
Dual Positive and Negative Regulation of Wingless Signaling by Adenomatous Polyposis Coli
Takacs, C. M., Baird, J. R., Hughes, E. G., Kent, S. S., Benchabane, H., Paik, R., & Ahmed, Y. F. (2008) · Science · doi:10.1126/science.1151232 · Cited by 56
Abundance, complexation, and trafficking of Wnt/β-catenin signaling elements in response to Wnt3a
Yokoyama, N. N., Yin, D., & Malbon, C. C. (2007) · Journal of Molecular Signaling · doi:10.1186/1750-2187-2-11 · Cited by 60
“Previous results suggested that Wnt stimulation can promote Axin degradation in mammalian cell culture [ 49-51 ] and fly embryos [52].”
BackgroundYadav, V. K., & Ducy, P. F. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05312.x · Cited by 55
Distinct Roles for Wnt-4 and Wnt-11 During Retinoic Acid-Induced Neuronal Differentiation
Elizalde, C., Campa, V. M., Caro, M., Schlangen, K., Aransay, A. M., Vivanco, M. D., & Kypta, R. M. (2010) · Stem Cells · doi:10.1002/stem.562 · Cited by 58
CK1 in Developmental Signaling
Jiang, J. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2016.09.002 · Cited by 53
“In the presence of Wnt, the destruction complex is recruited to activated LRP5/6 through its binding to Axin, leading to inhibition of β-catenin phosphorylation, βcatenin stabilization in the cytoplasm, and Wnt pathway activation (Mao et al., 2001; Tamai et al., 2004).”
BackgroundPeterson-Nedry, W., Erdeniz, N., Kremer, S., Yu, J., Baig-Lewis, S., & Wehrli, M. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.05.521 · Cited by 54
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Self-citationInnate antimicrobial host defense in small intestinal Crohn's disease
Koslowski, M. J., Beisner, J., Stange, E. F., & Wehkamp, J. (2009) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2009.08.011 · Cited by 60
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“Low-density lipoprotein receptor-related protein 5 (LRP5) is a co-receptor for Wnt [5,6],”
BackgroundZhang, Z., Qin, Y., He, J., Huang, Q., Li, M., Hu, Y.-Q., & Liu, Y. (2005) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2005.00173.x · Cited by 53
Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding
Li, Y., Chen, J., Lu, W., McCormick, L. M., Wang, J., & Bu, G. (2005) · Journal of Cell Science · doi:10.1242/jcs.02651 · Cited by 53
“By using co-immunoprecipitation, several group reported that LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8 (Tamai et al., 2000; Mao et al., 2001; Kato et al., 2002; Itasaki et al., 2003; Liu et al., 2003).”
BackgroundSelf-citationNoncanonical Wnt signaling promotes apoptosis in thymocyte development
Liang, H., Coles, A. H., Zhu, Z., Zayas, J., Jurecic, R., Kang, J., & Jones, S. N. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062692 · Cited by 52
Nusse, R. (2005) · Nature · doi:10.1038/438747a · Cited by 52
Jeong, W., & Jho, E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.714330 · Cited by 54
Huang, T., Xie, Z., Wang, J., Li, M., Jing, N., & Li, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.251165 · Cited by 54
Self-citationAlarcón, M. A., Medina, M. A., Hu, Q., Ávila, M. E., Bustos, B. I., Pérez‐Palma, E., Peralta, A. B., Salazar, P. L., Ugarte, G. D., Reyes, A. E., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.004 · Cited by 49
“amino acids Phe151 to Arg216 in the LRP6 protein alters the first and second b-propeller domains of the receptor, which have been previously found to be necessary for Wnt ligand presentation (He et al., 2004; Mao et al., 2001).”
BackgroundTumor microenvironment pathways: Cross regulation in breast cancer metastasis
Malla, R. R., & Kiran, P. J. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.11.015 · Cited by 52
Primary cilia in pancreatic development and disease
Lodh, S., O’Hare, E. A., & Zaghloul, N. A. (2014) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.21063 · Cited by 51
“P A A uthor M anuscript 1996; Hsieh et al., 1999; Tamai et al., 2000; Umbhauer et al., 2000; Mao et al., 2001).”
BackgroundTMEM59 potentiates Wnt signaling by promoting signalosome formation
Gerlach, J. P., Jordens, I., Tauriello, D. V. F., Kuper, I., Bugter, J. M., Noordstra, I., van der Kooij, J., Low, T. Y., Pimentel‐Muiños, F. X., Xanthakis, D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721321115 · Cited by 50
“Full-blown Wnt signaling requires activation of both FZD and LRP6 coreceptors (10, 50, 51).”
BackgroundCarayol, N., & Wang, C. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.02.014 · Cited by 50
Urano, T., Narusawa, K., Shiraki, M., Usui, T., Sasaki, N., Hosoi, T., Ouchi, Y., Nakamura, T., & Inoue, S. (2007) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-007-0757-9 · Cited by 50
“Further, low-density lipoprotein (LDL)-receptorrelated protein 5 and 6 (LRP5/6) were also found to be required for Wnt coreceptors [14,15].”
Background
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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