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Wg/Wnt Signal Can Be Transmitted through Arrow/LRP5,6 and Axin Independently of Zw3/Gsk3β Activity
Open accessAbstract
Activation of the Wnt signaling cascade provides key signals during development and in disease. Here we provide evidence, by designing a Wnt receptor with ligand-independent signaling activity, that physical proximity of Arrow (LRP) to the Wnt receptor Frizzled-2 triggers the intracellular signaling cascade. We have uncovered a branch of the Wnt pathway in which Armadillo activity is regulated concomitantly with the levels of Axin protein. The intracellular pathway bypasses Gsk3beta/Zw3, the kinase normally required for controlling beta-catenin/Armadillo levels, suggesting that modulated degradation of Armadillo is not required for Wnt signaling. We propose that Arrow (LRP) recruits Axin to the membrane, and that this interaction leads to Axin degradation. As a consequence, Armadillo is no longer bound by Axin, resulting in nuclear signaling by Armadillo.
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“It is important to note that Wnt stimulation also regulates the stability of Axin for with Wnt stimulation a de-phosphorylation of Axin and a decrease in cytoplasmic levels of Axin has been documented.29–31”
From Wnt signal transduction pathways (2008) · cites this paper as [29]
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Hendriksen, J., Jansen, M., Brown, C. M., van der Velde, H., van Ham, M., Galjart, N., Offerhaus, G. J. A., Fagotto, F., & Fornerod, M. W. J. (2008) · Journal of Cell Science · doi:10.1242/jcs.025536 · Cited by 76
“This suggests that an increase in Armadillo at the plasma membrane is also important for endogenous Wg signaling in the fruit fly.”
BackgroundInfluentialAxin Utilizes Distinct Regions for Competitive MEKK1 and MEKK4 Binding and JNK Activation
Luo, W., Ng, W. W., Jin, L., Ye, Z., Han, J., & Lin, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305277200 · Cited by 76
Endocytic trafficking of Wingless and its receptors, Arrow and DFrizzled-2, in the Drosophila wing
Rives, A. F., Rochlin, K. M., Wehrli, M., Schwartz, S. L., & DiNardo, S. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.02.006 · Cited by 74
“Since endogenous Arrow and DFz2 are not easily detectable near the D/V boundary where Wg puncta are visible, we used epitope-tagged Arrow (Arrow-HA) and DFz2 (DFz2-Myc; Tolwinski et al., 2003) to monitor receptor endocytosis.”
MethodInfluentialSelf-citationWingless Signaling: A Genetic Journey from Morphogenesis to Metastasis
Bejsovec, A. (2018) · Genetics · doi:10.1534/genetics.117.300157 · Cited by 74
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
Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta
Smalley, M. J., Signoret, N. Y. M., Robertson, D. M., Tilley, A., Hann, A. C., Ewan, K., Ding, Y., Paterson, H., & Dale, T. C. (2005) · Journal of Cell Science · doi:10.1242/jcs.02647 · Cited by 73
“This results in recruitment of axin to the LRP protein and Dishevelled to the Frizzled receptor (Cong et al., 2004; Mao et al., 2001; Tolwinski et al., 2003).”
BackgroundInteraction 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
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
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
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 data to suggest that axin interactswith the intracellular domain of LRP5 in vitro and in vivo, and the addition of Wnt-1 appears to stimulate the recruitment of axin to LRP5 at the membrane, where axin is degraded, which subsequently results in increased b-catenin levels and signaling [Mao et al., 2001; Tolwi…”
BackgroundIdentification and Characterization of Wnt Signaling Pathway in Keloid Pathogenesis
Igota, S., Tosa, M., Murakami, M., Egawa, S., Shimizu, H., Hyakusoku, H., & Ghazizadeh, M. (2013) · International Journal of Medical Sciences · doi:10.7150/ijms.5349 · Cited by 69
Dickkopf-1: a suitable target for the management of myeloma bone disease
Gavriatopoulou, M., Dimopoulos, M. A., Christoulas, D., Migkou, M., Iakovaki, M., Gkotzamanidou, M. A., & Terpos, E. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903025770 · Cited by 69
“Glycogen synthase kinase 3 (GSK3) is, after forming a complex with axin and adenomatous polyposis coli (APC), capable of phosphorylating β-catenin thus labelling it for proteasomal degradation [13-16].”
BackgroundInfluentialLRP8 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.”
ResultInfluentialStructural 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
Self-citationHaack, F., Lemcke, H., Ewald, R., Rharass, T., & Uhrmacher, A. M. (2015) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1004106 · Cited by 66
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
Ligand-Independent Traffic of Notch Buffers Activated Armadillo in Drosophila
Sanders, P., Descalzo, S. M., Balayo, T., Wirtz‐Peitz, F., Hayward, P. C., & Arias, A. M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000169 · Cited by 65
The role of the cysteine‐rich domain of Frizzled in Wingless‐Armadillo signaling
Povelones, M., & Nusse, R. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600817 · Cited by 65
“…of Wg protein. wgHfzDCRD requires arr to activate Arm signaling Wg is thought to activate Arm signaling by bridging the two membrane coreceptors Fz and Arr and bringing together their associated intracellular signaling components (Tamai et al, 2000; Tolwinski et al, 2003; Cong et al, 2004).”
BackgroundChen, 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
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).”
BackgroundThe 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
“co-receptors LRP5/6 and Fz, a series of biochemical reactions leads to recruitment of Axin to the plasma membrane and dissociation of the destruction complex (Mao et al., 2001; Cliffe et al., 2003; Tolwinski et al., 2003).”
BackgroundNormal morphogenesis of epithelial tissues and progression of epithelial tumors
Wang, C., Jamal, L., & Janes, K. A. (2011) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.159 · Cited by 65
Papadopoulou, D., Bianchi, M. W., & Bourouis, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4909-4919.2004 · Cited by 60
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
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
“Although there is no direct evidence that these proteins interact (Wu and Nusse, 2002), a chimeric molecule that artificially fused the extracellular and transmembrane portions of Fz with the cytosolic domain of Arrow produced constitutive pathway activity (Tolwinski et al., 2003).”
BackgroundJiang, N., Chen, W., Zhang, J.-W., Xu, C., Zeng, X., Zhang, T., Li, Y., & Wang, G. (2015) · Oncotarget · doi:10.18632/oncotarget.3492 · Cited by 58
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BackgroundRui, Y., Xu, Z., Xiong, B., Cao, Y., Lin, S., Zhang, M., Chan, S.-C., Luo, W., Han, Y., Ye, Z., et al. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.07.006 · 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
“Although Axin plays an important role in the degradation of -catenin through the ubiquitin-proteasome pathway and is itself subject to degradation following a Wnt signal (10, 11, 27, 28 ), the ubiquitination of Axin has not been previously reported.”
BackgroundDual 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].”
BackgroundLong‐term in vitro analysis of limb cartilage development: Involvement of Wnt signaling
Daumer, K. M., Tufan, A. C., & Tuan, R. S. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20190 · Cited by 55
“E-mail: tuanr@mail.nih.gov Received 22 January 2004; Accepted 7 May 2004 DOI 10.1002/jcb.20190 et al., 2003; Tolwinski et al., 2003], Wnts are thought to mediate several effectors in a localized signaling cascade resulting in the regulation of cell adhesion and/or gene expression.”
BackgroundInfluentialPeterson-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
Self-citationMesd 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
“The cytoplasmic domains of LRP5/6, upon receptor activation by Wnt proteins, recruit the cytosolic scaffold protein axin to the membrane, therefore preventing it from participation in the degradation of -catenin (Mao et al., 2001; Liu et al., 2003; Tolwinski et al., 2003; Tamai et al., 2004).”
BackgroundNusse, R. (2005) · Nature · doi:10.1038/438747a · Cited by 52
Pancratov, R., Peng, F., Smibert, P., Yang, J.-S., Olson, E., Guha-Gilford, C., Kapoor, A., Liang, F.-X., Lai, E., Flaherty, M. S., et al. (2013) · Development · doi:10.1242/dev.092817 · Cited by 47
Li, B., Orton, D., Neitzel, L. R., Astudillo, L., Shen, C., Long, J., Chen, X., Kirkbride, K. C., Doundoulakis, T., Guerra, M. L., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aak9916 · Cited by 51
p15RS Attenuates Wnt/β-Catenin Signaling by Disrupting β-Catenin·TCF4 Interaction
Wu, Y., Zhang, Y., Zhang, H., Yang, X., Wang, Y., Ren, F., Huitu, L., Zhai, Y., Jia, B., Yu, J. Q., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.148791 · Cited by 48
Nishiya, N., Oku, Y., Kumagai, Y., Sato, Y., Yamaguchi, E., Sasaki, A., Shoji, M., Ohnishi, Y., Okamoto, H., & Uehara, Y. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.02.015 · Cited by 47
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Gloushankova, N. A. (2008) · Biochemistry (Moscow) · doi:10.1134/s000629790807002x · Cited by 45
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Hsieh, J.-C. (2004) · Frontiers in bioscience · doi:10.2741/1321 · Cited by 46
Wnt, Hedgehog and Junctional Armadillo/β-Catenin Establish Planar Polarity in the Drosophila Embryo
Colosimo, P. F., & Tolwinski, N. S. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000009 · Cited by 45
“, is the most useful, because it loses most of its ability to function as a transcriptional activator (shown here by loss of naked cuticle), though mutant protein levels are high and junctions appear normal”
BackgroundSelf-citationMultiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6
Wolf, J., Palmby, T. R., Gavard, J., Williams, B. O., & Gutkind, J. S. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.12.013 · Cited by 45
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“In the fly, a chimeric molecule fusing full-length Fz with the cytosolic domain of Arr produces ligand-independent pathway activity (Tolwinski et al., 2003).”
BackgroundBaig-Lewis, S., Peterson-Nedry, W., & Wehrli, M. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.03.005 · Cited by 42
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BackgroundMethodResultInfluentialSelf-citationSignalling activity of beta-catenin targeted to different subcellular compartments
Hagen, T., Sethi, J. K., Foxwell, N., & Vidal‐Puig, A. (2004) · Biochemical Journal · doi:10.1042/bj20031749 · Cited by 42
Regulation of Wnt Signalling by Receptor-mediated Endocytosis
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Notch synergizes with axin to regulate the activity of armadillo in Drosophila
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“In agreement with previous observations, Notch does not need Shaggy to modulate Wnt signalling (Hayward et al., 2005) but it appears to be closely associated with a function of Axin that modulates Armadillo activity rather than its amount (Tolwinski et al., 2003).”
BackgroundInfluentialWang, Z., Tian, A., Benchabane, H., Tacchelly‐Benites, O., Yang, E., Nojima, H., & Ahmed, Y. F. (2016) · Development · doi:10.1242/dev.127647 · Cited by 39
“However, the existing Axin antibodies did not allow detection of endogenous Axin in immunoblots, which was a presumed consequence of the very low Axin concentration (Tolwinski et al., 2003; Willert et al., 1999).”
BackgroundKaur, P., Saunders, T. E., & Tolwinski, N. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-16879-0 · Cited by 38
Self-citationDasGupta, R., Nybakken, K. E., Booker, M. A., Mathey-Prévôt, B., Gonsalves, F. C., Changkakoty, B., & Perrimon, N. (2007) · Genome biology · doi:10.1186/gb-2007-8-9-r203 · Cited by 38
“Recent studies have suggested that constitutively activated ΔNLrp6 or a chimera between the Frizzled2 (Dfz2) receptor and intracellular cytoplasmic tail of the Drosophila ortholog of Lrp6 (encoded by the arrow (arr) gene) can activate the Wg pathway in a ligand-, GSK-3β-, and disheveled (dsh)-independent manner [34].”
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Willems, B., Tao, S., Yu, T., Huysseune, A., Witten, P. E., & Winkler, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131768 · Cited by 37
Michiue, T., Fukui, A., Yukita, A., Sakurai, K., Danno, H., Kikuchi, A., & Asashima, M. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20037 · Cited by 36
“It was also shown by Drosophila analysis that canonical signaling transmitted through LRP–Axin interaction (Tolwinski et al., 2003).”
BackgroundLu, J., Zhang, F., Zhao, D., Hong, L., Min, J., Zhang, L., Li, F., Yan, Y., Li, H., Ma, Y., et al. (2008) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9518-4 · Cited by 35
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Colosimo, P. F., Liu, X., Kaplan, N., & Tolwinski, N. S. (2009) · Developmental Dynamics · doi:10.1002/dvdy.21963 · Cited by 36
“Embryos were fixed with Heat-Methanol treatment (Muller and Wieschaus, 1996) or with heptane/4% formaldehyde in phosphate buffer (0.1 M Na3PO4 pH 7.4; Tolwinski et al., 2003).”
MethodInfluentialSelf-citationDestruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions inin vivo
Lybrand, D. B., Naiman, M., Laumann, J. M., Boardman, M., Petshow, S., Hansen, K., Scott, G. D., & Wehrli, M. (2019) · Development · doi:10.1242/dev.164145 · Cited by 34
“The physical interaction of Axin with the Wnt co-receptor LRP5/LRP6 (Arrow, in Drosophila; Mao et al., 2001, Tolwinski et al., 2003) depends on phosphorylation of LRP5/LRP6/Arrow by GSK3β/Sgg (Zhang et al., 2006; Zeng et al., 2008; Davidson et al., 2005; Bilic et al., 2007; Cliffe et al., 2003;…”
BackgroundSelf-citationZhu, B., Xue, F., Li, G., & Zhang, C. (2019) · Cell Proliferation · doi:10.1111/cpr.12709 · Cited by 33
Complex Interactions between GSK3 and aPKC in Drosophila Embryonic Epithelial Morphogenesis
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Self-citationPovelones, M., Howes, R., Fish, M., & Nusse, R. (2005) · Genetics · doi:10.1534/genetics.105.045245 · Cited by 32
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“When Wnt proteins are present, the so-called Wnt-on state, the Wnt ligands bind to FZD and LRP5/6 on the cell membrane [21, 22].”
BackgroundDescalzo, S. M., Tkocz, K., Balayo, T., & Arias, A. M. (2011) · Development · doi:10.1242/dev.061309 · Cited by 32
Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review)
Wang, X., Huai, G., Wang, H., Liu, Y., Qi, P., Shi, W. Q., Peng, J., Yang, H., Deng, S., & Wang, Y. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.3352 · Cited by 31
“Phosphorylated β-catenin promotes degradation of taZ via interaction with YaP/taZ. sfrP1 inhibits β-catenin, which is inhibited by GSK3β and induces oHt, resulting in primary open-angle glaucoma. tead, transcriptional enhancer factor tef-1; aPc, adenomatous polyposis coli; GSK3, glycogen synthase kinase 3; cK1, casein…”
BackgroundInfluentialKennell, J. A., & Cadigan, K. M. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-1145-2_1 · Cited by 31
The structure of Wntch signalling and the resolution of transition states in development
Muñoz‐Descalzo, S., & Arias, A. M. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.01.012 · Cited by 31
“Although the mantra of Wnt signalling links directly the levels of cytosolic ß-catenin to its transcriptional function, there is abundant evidence that this association is weak [19-25].”
Hedgehog Signaling: Costal-2 Bridges the Transduction Gap
Kalderon, D. (2004) · Current Biology · doi:10.1016/j.cub.2003.12.047 · Cited by 31
Casein Kinase 1α as a Regulator of Wnt-Driven Cancer
Shen, C., Nayak, A., Meléndez, R. A., Wynn, D. T., Jackson, J., Lee, E. N., Ahmed, Y. F., & Robbins, D. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165940 · Cited by 31
“In response to Wnt ligands, components of the destruction complex are recruited to the plasma membrane, where axin interacts with LRP5/6 to promote signalosome formation and subsequent activation [17,42,43].”
BackgroundThreonine 393 of β‐catenin regulates interaction with Axin
Wu, H., Symes, K., Seldin, D. C., & Dominguez, I. M. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22260 · Cited by 31
“C57MG cells, an immortalized nontransformed murine breast epithelial cell line [Vaidya et al., 1978], was chosen for these experiments, as canonical Wnt signaling is activated in response to Wnts [Giarre et al., 1998; Shibamoto et al., 1998] and activating mutations of b-catenin [Staal et al.,…”
MethodBalmer, S., Dussert, A., Collu, G. M., de Gracia, E. B., Iomini, C., & Mlodzik, M. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.07.016 · Cited by 28
“A Fz2-Arr chimeric protein, in which full length Fz2 is fused to the cytoplasmic tail of Arr, constitutes an activated form of the two receptors (Tolwinski et al., 2003).”
BackgroundTomchaney, M., Mysore, K., Sun, L., Li, P., Emrich, S., Severson, D. W., & Duman‐Scheel, M. (2014) · Biology of Sex Differences · doi:10.1186/s13293-014-0010-x · Cited by 30
“Components of critical developmental signaling cascades, including cubitus interruptus (ci), a member of the Hedgehog signaling pathway (reviewed by [33]), as well as arrow, a component of the Wnt/Wingless (Wg) signaling pathway [34], are upregulated in the developing female pupal brain (Figure 4B,E, Additional file 1…”
BackgroundAxin phosphorylation in both Wnt-off and Wnt-on states requires the tumor suppressor APC
Tacchelly‐Benites, O., Wang, Z., Yang, E., Benchabane, H., Tian, A., Randall, M. P., & Ahmed, Y. F. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007178 · Cited by 29
A conserved role for arrow in posterior axis patterning across Arthropoda
Setton, E. V. W., & Sharma, P. P. (2021) · Developmental Biology · doi:10.1016/j.ydbio.2021.02.006 · Cited by 28
“…( β -catenin) to avoid degradation, enter the nucleus, and begin transcription of genes under control of Pangolin (Pan; vertebrate homolog: TCF) (Tolwinski et al., 2003; Logan and Nusse 2004; Cadigan and Liu 2006; Peterson-Nedry et al., 2008; Cadigan and Waterman 2012; Lybrand et al., 2019).”
BackgroundWang, Z., Tacchelly‐Benites, O., Yang, E., Thorne, C. A., Nojima, H., Lee, E. N., & Ahmed, Y. F. (2016) · Genetics · doi:10.1534/genetics.115.183244 · Cited by 27
RacGap50C Negatively Regulates Wingless Pathway Activity During Drosophila Embryonic Development
Jones, W. M., & Bejsovec, A. (2005) · Genetics · doi:10.1534/genetics.104.039735 · Cited by 26
“We find similar interactions with Axin, another negative regulator of the Wg pathway.”
BackgroundInfluentialDestruction of a Destructor: A New Avenue for Cancer Therapeutics Targeting the Wnt Pathway
Liu, C., & He, X. (2009) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp040 · Cited by 26
“Because Axin is a concentration-limiting component for the assembly of the destruction complex, Axin abundance has profound influence on Wnt/b-catenin signaling (Lee et al., 2003; Tolwinski et al., 2003).”
Emam, S. M., & Moussa, N. (2024) · BDJ Open · doi:10.1038/s41405-024-00211-w · Cited by 25
“The cytoplasmic tail of LRP co-receptor may interact directly with Axin [77].”
BackgroundDibus, N., Liďák, T., & C̆ermák, L. (2019) · Genes · doi:10.3390/genes10100815 · Cited by 27
“In more detail, the intracellular signaling is triggered by Wnt binding to the complex of its receptor Frizzled (Fzd) and co-receptor from the lipoprotein receptor-related protein family (LRP5/6) [37].”
BackgroundEpithelial Polarity: Interactions Between Junctions and Apical–Basal Machinery
Kaplan, N., Liu, X., & Tolwinski, N. S. (2009) · Genetics · doi:10.1534/genetics.109.108878 · Cited by 26
Self-citationWaldrop, S., Chan, C., Çağatay, T., Zhang, S., Rousset, R., Mack, J., Zeng, W., Fish, M., Zhang, M., Amanai, M., et al. (2006) · Genetics · doi:10.1534/genetics.106.061853 · Cited by 26
Hamartin and tuberin modulate gene transcription via β-catenin
Jóźwiak, J., & Wlodarski, P. K. (2006) · Journal of Neuro-Oncology · doi:10.1007/s11060-006-9134-0 · Cited by 23
“LRP is a long single pass protein whose cytoplasmic tail recruits Axin to the membrane, which leads to Axin degradation [6].”
BackgroundNHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia
Georgescu, M., Gagea, M., & Cote, G. J. (2016) · Neoplasia · doi:10.1016/j.neo.2016.07.003 · Cited by 22
“They activate the pathway by disassembling the cytoplasmic destruction complex formed by axin, Apc, GSK-3β, CK1α/ε, and β-catenin [5,6].”
BackgroundRole of the Wnt/β-Catenin Pathway in Renal Osteodystrophy
Bisson, S.-K., Ung, R., & Mac‐Way, F. (2018) · International Journal of Endocrinology · doi:10.1155/2018/5893514 · Cited by 21
“Upon binding of one of these ligands, Fz and Lrp5/6 are brought together [20].”
BackgroundDiversity of axin in signaling pathways and its relation to colorectal cancer
Parveen, N., Hussain, M. U., Pandith, A. A., & Mudassar, S. (2010) · Medical Oncology · doi:10.1007/s12032-010-9722-x · Cited by 20
“Interestingly, axin itself is regulated with its stability being modulated by Wnt receptors [ 42 ], Dvl [49], and phosphorylation by GSK-3b [50].”
BackgroundBoucsein, A., Benzler, J., Hempp, C., Stöhr, S., Helfer, G., & Tups, A. (2015) · Endocrinology · doi:10.1210/en.2015-1708 · Cited by 20
Dual Roles for Membrane Association of Drosophila Axin in Wnt Signaling
Wang, Z., Tacchelly‐Benites, O., Yang, E., & Ahmed, Y. F. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006494 · Cited by 20
Rauschenberger, V., Bernkopf, D. B., Krenn, S., Jalal, K., Heller, J., Behrens, J., Gentzel, M., & Schambony, A. (2017) · Development · doi:10.1242/dev.144477 · Cited by 22
“Pgam5 physically interacts with Arrb2 and Dvl2.”
BackgroundInfluentialAxin Family of Scaffolding Proteins in Development: Lessons from C. elegans
Mallick, A., Taylor, S. K. B., Ranawade, A., & Gupta, B. P. (2019) · Journal of Developmental Biology · doi:10.3390/jdb7040020 · Cited by 20
Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling
Sheremet, M., Kapoor, S., Schröder, P., Kumar, K., Ziegler, S., & Waldmann, H. (2017) · ChemBioChem · doi:10.1002/cbic.201700260 · Cited by 19
Eugenol exposure inhibits embryonic development and swim bladder formation in zebrafish
Tao, Y., Du, C., Duan, B., Wang, W., Guo, H., Feng, J., Xu, H., & Li, Y. (2023) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2023.109602 · Cited by 19
Benchabane, H., Hughes, E. G., Takacs, C. M., Baird, J. R., & Ahmed, Y. F. (2008) · Development · doi:10.1242/dev.013805 · Cited by 21
Metadata
- Authors
- Tolwinski, N. S., Wehrli, M., Rives, A., Erdeniz, N., DiNardo, S., & Wieschaus, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Oregon Health & Science University (US)
- University of Pennsylvania (US)
- Corresponding author
- Wieschaus, Eric
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 4
- Issue
- 3
- Pages
- 407-418
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2037128138
- Cited by
- 286
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 7 · 2018: 7 · 2017: 14 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 11 · 2012: 18
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3791 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM45747, PO1CA41086, F32GM20342)
- Howard Hughes Medical Institute
- National Science Foundation
- 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 › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- Wnt signaling, Axin, GSK3β, Frizzled-2, ligand-independent signaling, Wnt receptors
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Carrier Proteins, Drosophila melanogaster, Embryo, Nonmammalian, Female, Membrane Proteins, Mutation, Proto-Oncogene Proteins, Receptors, Cell Surface, Receptors, LDL, Recombinant Fusion Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Gene Expression Regulation, Developmental, Active Transport, Cell Nucleus, LDL-Receptor Related Proteins, Drosophila Proteins, Glycogen Synthase Kinase 3, Receptors, G-Protein-Coupled, Adaptor Proteins, Signal Transducing, Wnt1 Protein, Frizzled Receptors, Armadillo Domain Proteins, Low Density Lipoprotein Receptor-Related Protein-5
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