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Research Article

The way Wnt works: Components and mechanism

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Pages 1-31 | Received 02 Oct 2012, Accepted 21 Nov 2012, Published online: 21 Dec 2012

References

  • Ahmed Y, Nouri A, Wieschaus E. 2002. Drosophila Apc1 and Apc2 regulate Wingless transduction throughout development. Development. 129:1751–1762.
  • Ahn Victoria,E, Chu MatthewL-H, Choi H-J, Tran D, Abo A, Weis WilliamI. 2011. Structural basis of Wnt signaling inhibition by Dickkopf Binding to LRP5/6. Dev Cell. 21:862–873.
  • Akiri G, Cherian MM, Vijayakumar S, Liu G, Bafico A, Aaronson SA. 2009. Wnt pathway aberrations including autocrine Wnt activation occur at high frequency in human non-small-cell lung carcinoma. Oncogene. 28:2163–2172.
  • Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, Alkalay I. 2002. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: A molecular switch for the Wnt pathway. Genes Dev. 16:1066–1076.
  • Angers S, Thorpe CJ, Biechele TL, Goldenberg SJ, Zheng N, MacCoss MJ, Moon RT. 2006. The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nat Cell Biol. 8:348–357.
  • Awakura Y, Nakamura E, Ito N, Kamoto T, Ogawa O. Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncol Rep. 2008a; 20:1257–1263.
  • Awakura Y, Nakamura E, Ito N, Kamoto T, Ogawa O. Methylation-associated silencing of SFRP1 in renal cell carcinoma. Oncol Rep. 2008b; 20:1257–1263.
  • Baeg GH, Lin X, Khare N, Baumgartner S, Perrimon N. 2001. Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless. Development. 128:87–94.
  • Baeg GH, Selva EM, Goodman RM, Dasgupta R, Perrimon N. 2004. The Wingless morphogen gradient is established by the cooperative action of Frizzled and heparan sulfate proteoglycan receptors. Dev Biol. 276:89–100.
  • Bafico A, Liu G, Goldin L, Harris V, Aaronson SA. 2004. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell. 6:497–506.
  • Baig-Lewis S, Peterson-Nedry W, Wehrli M. 2007. Wingless/Wnt signal transduction requires distinct initiation and amplification steps that both depend on Arrow/LRP. Dev Biol. 306:94–111.
  • Bänziger C, Soldini D, Schütt C, Zipperlen P, Hausmann G, Basler K. 2006. Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell. 125:509–522.
  • Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 449:1003–1007.
  • Battagli C, Uzzo RG, Dulaimi E, Ibanez de Caceres I, Krassenstein R, Al-Saleem T, Greenberg RE, Cairns P. 2003. Promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients. Cancer Res. 63:8695–8699.
  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. 1996. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 382:638–642.
  • Bejsovec A, Wieschaus E. 1995. Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics. 139:309–320.
  • Belenkaya TY, Han C, Standley HJ, Lin X, Houston DW, Heasman J. 2002. Pygopus encodes a nuclear protein essential for wingless/Wnt signaling. Development. 129:4089–4101.
  • Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R. 1996. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 382:225–230.
  • Bienz M. 2002. The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol. 3:328–338.
  • Bilić J, Huang Y-L, Davidson G, Zimmermann T, Cruciat C-M, Bienz M, Niehrs C. 2007. Wnt induces LRP6 signalosomes and promotes Dishevelled-dependent LRP6 phosphorylation. Science. 316:1619–1622.
  • Binari RC, Staveley BE, Johnson WA, Godavarti R, Sasisekharan R, Manoukian AS. 1997. Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling. Development. 124:2623–2632.
  • Bjorklund P, Svedlund J, Olsson AK, Akerstrom G, Westin G. 2009. The internally truncated LRP5 receptor presents a therapeutic target in breast cancer. PLoS One. 4:e4243.
  • Blauwkamp TA, Chang MV, Cadigan KM. 2008. Novel TCF-binding sites specify transcriptional repression by Wnt signalling. EMBO J. 27:1436–1446.
  • Bourhis E, Tam C, Franke Y, Bazan JF, Ernst J, Hwang J, Costa M, Cochran AG, Hannoush RN. 2010. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 285:9172–9179.
  • Bovolenta P, Esteve P, Ruiz JM, Cisneros E, Lopez-Rios J. 2008. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J Cell Sci. 121:737–746.
  • Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 346:1513–1521.
  • Bradley RS, Brown AM. 1990. The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. EMBO J. 9:1569–1575.
  • Brons IGM, Smithers LE, Trotter MWB, Rugg-Gunn P, Sun B, Lopes SMCdS, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L. 2007. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature. 448:191–195.
  • Buechling T, Chaudhary V, Spirohn K, Weiss M, Boutros M. 2011. p24 proteins are required for secretion of Wnt ligands. EMBO Rep. 12:1265–1272.
  • Cadigan KM. 2012. TCFs and Wnt/beta-catenin signaling: More than one way to throw the switch. Curr Top Dev Biol. 98:1–34.
  • Cadigan KM, Peifer M. 2009. Wnt signaling from development to disease: Insights from model systems. Cold Spring Harb Perspect Biol. 1:a002881.
  • Callow MG, Tran H, Phu L, Lau T, Lee J, Sandoval WN, Liu PS, Bheddah S, Tao J, Lill JR, Hongo J-A, Davis D, Kirkpatrick DS, Polakis P, Costa M. 2011. Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PLoS One. 6:e22595.
  • Capurro MI, Xiang YY, Lobe C, Filmus J. 2005. Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res. 65:6245–6254.
  • Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. 2011. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proc Natl Acad Sci USA. 108:11452–11457.
  • Chan EF, Gat U, McNiff JM, Fuchs E. 1999. A common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet. 21:410–413.
  • Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan C-W, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L. 2009. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 5:100–107.
  • Chen S, Bubeck Bryan D, MacDonald T, Liang W-X, Mao J-H, Malinauskas T, Llorca O, Aricescu AR, Siebold C, He X, Jones EY. 2011. Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling. Dev Cell. 21:848–861.
  • Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W. 2011. Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol. 18:1204–1210.
  • Cong F, Varmus H. 2004. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin. Proc Natl Acad Sci USA. 101:2882–2887.
  • Cong F, Schweizer L, Varmus H. Casein kinase Iepsilon modulates the signaling specificities of dishevelled. Mol Cell Biol. 2004a; 24:2000–2011.
  • Cong F, Schweizer L, Varmus H. Wnt signals across the plasma membrane to activate the β-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development. 2004b; 131:5103–5115.
  • Coudreuse DYM, Roël G, Betist MC, Destrée O, Korswagen HC. 2006. Wnt gradient formation requires retromer function in Wnt-producing cells. Science. 312:921–924.
  • Couso JP, Bate M, Martinez-Arias A. 1993. A wingless-dependent polar coordinate system in Drosophila imaginal discs. Science. 259:484–489.
  • Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:785–789.
  • Cselenyi CS, Jernigan KK, Tahinci E, Thorne CA, Lee LA, Lee E. 2008. LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of β-catenin. Proc Nat Acad Sci. 105:8032–8037.
  • Cuilliere-Dartigues P, El-Bchiri J, Krimi A, Buhard O, Fontanges P, Flejou JF, Hamelin R, Duval A. 2006. TCF-4 isoforms absent in TCF-4 mutated MSI-H colorectal cancer cells colocalize with nuclear CtBP and repress TCF-4-mediated transcription. Oncogene. 25:4441–4448.
  • Dahmen RP, Koch A, Denkhaus D, Tonn JC, Sörensen N, Berthold F, Behrens J, Birchmeier W, Wiestler OD, Pietsch T. 2001. Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res. 61:7039–7043.
  • Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH. 2001. Crystal structure of glycogen synthase kinase 3 beta: Structural basis for phosphate-primed substrate specificity and autoinhibition. Cell. 105:721–732.
  • Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH. 2003. Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex. EMBO J. 22:494–501.
  • Daniels DL, Weis WI. 2005. Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol. 12:364–371.
  • DasGupta R, Kaykas A, Moon RT, Perrimon N. 2005. Functional genomic analysis of the Wnt-wingless signaling pathway. Science. 308:826–833.
  • Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C. 2005. Casein kinase 1 [gamma] couples Wnt receptor activation to cytoplasmic signal transduction. Nature. 438:867–872.
  • Davidson G, Shen J, Huang YL, Su Y, Karaulanov E, Bartscherer K, Hassler C, Stannek P, Boutros M, Niehrs C. 2009. Cell cycle control of wnt receptor activation. Dev Cell. 17:788–799.
  • de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C. 1998. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Nat Acad Sci USA. 95:8847–8851.
  • de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es JE, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H. 2011. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature. 476:293–297.
  • Ding VW, Chen RH, McCormick F. 2000. Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J Biol Chem. 275:32475–32481.
  • Doble BW, Patel S, Wood GA, Kockeritz LK, Woodgett JR. 2007. Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling shown by using an allelic series of embryonic stem cell lines. Dev Cell. 12:957–971.
  • Dominguez I, Itoh K, Sokol SY. 1995. Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc Natl Acad Sci USA. 92:8498–8502.
  • Dorsky RI, Sheldahl LC, Moon RT. 2002. A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development. Dev Biol. 241:229–237.
  • Dravid G, Ye Z, Hammond H, Chen G, Pyle A, Donovan P, Yu X, Cheng L. 2005. Defining the role of Wnt/β-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem Cells. 23:1489–1501.
  • Dubois L, Lecourtois M, Alexandre C, Hirst E, Vincent JP. 2001. Regulated endocytic routing modulates wingless signaling in Drosophila embryos. Cell. 105:613–624.
  • Eberhart CG, Tihan T, Burger PC. 2000. Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol. 59:333–337.
  • Egger-Adam D, Katanaev VL. 2009. The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway. Dev Dyn. 239:168–183.
  • Eguchi M, Nguyen C, Lee SC, Kahn M. 2005. ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription. Med Chem. 1:467–472.
  • Eisenmann, DM. Wnt signaling (June 25, 2005), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.7.1, http://www.wormbook.org.
  • Embi N, Rylatt DB, Cohen P. 1980. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 107:519–527.
  • Eugster C, Panakova D, Mahmoud A, Eaton S. 2007. Lipoprotein-heparan sulfate interactions in the Hh pathway. Dev Cell. 13:57–71.
  • Fagotto F, Jho E, Zeng L, Kurth T, Joos T, Kaufmann C, Costantini F. 1999. Domains of Axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization. J Cell Biol. 145:741–756.
  • Fagotto F, Funayama N, Gluck U, Gumbiner BM. 1996. Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus. J Cell Biol. 132:1105–1114.
  • Fagotto F, Gluck U, Gumbiner BM. 1998. Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin. Curr Biol. 8:181–190.
  • Farr GH3rd, Ferkey DM, Yost C, Pierce SB, Weaver C, Kimelman D. 2000. Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification. J Cell Biol. 148:691–702.
  • Faux MC, Coates JL, Catimel B, Cody S, Clayton AHA, Layton MJ, Burgess AW. 2008. Recruitment of adenomatous polyposis coli and |[beta]|-catenin to axin-puncta. Oncogene. 27:5808–5820.
  • Fiedler M, Sanchez-Barrena MJ, Nekrasov M, Mieszczanek J, Rybin V, Muller J, Evans P, Bienz M. 2008. Decoding of methylated histone H3 tail by the Pygo-BCL9 Wnt signaling complex. Mol Cell. 30:507–518.
  • Filmus J, Capurro M, Rast J. 2008. Glypicans. Genome Biol. 9:224.
  • Forde JE, Dale TC. 2007. Glycogen synthase kinase 3: A key regulator of cellular fate. Cell Mol Life Sci. 64:1930–1944.
  • Franch-Marro X, Marchand O, Piddini E, Ricardo S, Alexandre C, Vincent JP. 2005. Glypicans shunt the Wingless signal between local signalling and further transport. Development. 132:659–666.
  • Franch-Marro X, Wendler F, Guidato S, Griffith J, Baena-Lopez A, Itasaki N, Maurice MM, Vincent J-P. 2008. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nat Cell Biol. 10:170–177.
  • Fukui T, Kondo M, Ito G, Maeda O, Sato N, Yoshioka H, Yokoi K, Ueda Y, Shimokata K, Sekido Y. 2005. Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer. Oncogene. 24:6323–6327.
  • Gallet A, Staccini-Lavenant L, Therond PP. 2008. Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis. Dev Cell. 14:712–725.
  • Galli LM, Barnes TL, Secrest SS, Kadowaki T, Burrus LW. 2007. Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube. Development. 134:3339–3348.
  • Gao ZH, Seeling JM, Hill V, Yochum A, Virshup DM. 2002. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci USA. 99:1182–1187.
  • Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, Natrajan R, Reis-Filho JS. 2010. Beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation. Mod Pathol. 24:209–231.
  • Gilman AG. 1987. G proteins: Transducers of receptor-generated signals. Annu Rev Biochem. 56:615–649.
  • Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C. 2011. LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling. EMBO Rep. 12:1055–1061.
  • Goentoro L, Kirschner MW. 2009. Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling. Mol Cell. 36:872–884.
  • Goentoro L, Shoval O, Kirschner MW, Alon U. 2009. The incoherent feedforward loop can provide fold-change detection in gene regulation. Mol Cell. 36:894–899.
  • Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 107:513–523.
  • Gonzalez-Sancho JM, Brennan KR, Castelo-Soccio LA, Brown AM. 2004. Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 24:4757–4768.
  • Gottardi CJ, Gumbiner BM. 2004. Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes. J Cell Biol. 167:339–349.
  • Gottardi CJ, Wong E, Gumbiner BM. 2001. E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. J Cell Biol. 153:1049–1060.
  • Graham TA, Weaver C, Mao F, Kimelman D, Xu W. 2000. Crystal structure of a beta-catenin/Tcf complex. Cell. 103:885–896.
  • Gross JC, Chaudhary V, Bartscherer K, Boutros M. 2012. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 14:1036–1045.
  • Guger KA, Gumbiner BM. 1995. Beta-Catenin has Wnt-like activity and mimics the Nieuwkoop signaling center in Xenopus dorsal-ventral patterning. Dev Biol. 172:115–125.
  • Ha N-C, Tonozuka T, Stamos JL, Choi H-J, Weis WI. 2004. Mechanism of phosphorylation-dependent binding of APC to [beta]-catenin and its role in [beta]-catenin degradation. Mol Cell. 15:511–521.
  • Haar Et, Coll JT, Austen DA, Hsiao H-M, Swenson L, Jain J. 2001. Structure of GSK3|[beta]| reveals a primed phosphorylation mechanism. Nat Struct Mol Biol. 8:593–596.
  • Hacker U, Lin X, Perrimon N. 1997. The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis. Development. 124:3565–3573.
  • Hacker U, Nybakken K, Perrimon N. 2005. Heparan sulphate proteoglycans: The sweet side of development. Nat Rev Mol Cell Biol. 6:530–541.
  • Hadjihannas MV, Bernkopf DB, Bruckner M, Behrens J. 2012. Cell cycle control of Wnt/beta-catenin signalling by conductin/axin2 through CDC20. EMBO Rep. 13:347–354.
  • Haerry TE, Heslip TR, Marsh JL, O'Connor MB. 1997. Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. Development. 124:3055–3064.
  • Hamada F, Bienz M. 2004. The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell. 7:677–685.
  • Hammerlein A, Weiske J, Huber O. 2005. A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/beta-catenin complex. Cell Mol Life Sci. 62:606–618.
  • Han C, Belenkaya TY, Khodoun M, Tauchi M, Lin X. 2004. Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development. 131:1563–1575.
  • Han C, Yan D, Belenkaya TY, Lin X. 2005. Drosophila glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc. Development. 132:667–679.
  • Hanson AJ, Wallace HA, Freeman TJ, Beauchamp RD, Lee LA, Lee E. 2012. XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. Mol Cell. 45 (5): 619–628.
  • Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F. 2012. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 485:195–200.
  • Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. 1998. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol. 8:573–581.
  • Hatzis P, van der Flier LG, van Driel MA, Guryev V, Nielsen F, Denissov S, Nijman IJ, Koster J, Santo EE, Welboren W, Versteeg R, Cuppen E, van de Wetering M, Clevers H, Stunnenberg HG. 2008. Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells. Mol Cell Biol. 28:2732–2744.
  • Hay-Koren A, Caspi M, Zilberberg A, Rosin-Arbesfeld R. 2010. The EDD E3 ubiquitin ligase ubiquitinates and up-regulates beta-catenin. Mol Biol Cell. 22:399–411.
  • He X, Saint-Jeannet JP, Woodgett JR, Varmus HE, Dawid IB. 1995. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature. 374:617–622.
  • He X, Semenov M, Tamai K, Zeng X. 2004. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: Arrows point the way. Development. 131:1663–1677.
  • Heasman J, Crawford A, Goldstone K, Garner-Hamrick P, Gumbiner B, McCrea P, Kintner C, Noro CY, Wylie C. 1994. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell. 79:791–803.
  • Heath JP. 1996. Epithelial cell migration in the intestine. Cell Biol Int. 20:139–146.
  • Henderson BR, Fagotto F. 2002. The ins and outs of APC and beta-catenin nuclear transport. EMBO Rep. 3:834–839.
  • Hendriksen J, Fagotto F, van der Velde H, van Schie M, Noordermeer J, Fornerod M. 2005. RanBP3 enhances nuclear export of active (beta)-catenin independently of CRM1. J Cell Biol. 171:785–797.
  • Hendriksen J, Jansen M, Brown CM, van der Velde H, van Ham M, Galjart N, Offerhaus GJ, Fagotto F, Fornerod M. 2008. Plasma membrane recruitment of dephosphorylated beta-catenin upon activation of the Wnt pathway. J Cell Sci. 121:1793–1802.
  • Henderson WRJr, Chi EY, Ye X, Nguyen C, Tien YT, Zhou B, Borok Z, Knight DA, Kahn M. 2010. Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis. Proc Natl Acad Sci USA. 107:14309–14314.
  • Hernandez AR, Klein AM, Kirschner MW. 2012. Kinetic responses of beta-catenin specify the sites of Wnt control. Science. 338:1337–1340.
  • Herr P, Basler K. 2011. Porcupine-mediated lipidation is required for Wnt recognition by Wls. Dev Biol. 361:392–402.
  • Herzig M, Savarese F, Novatchkova M, Semb H, Christofori G. 2007. Tumor progression induced by the loss of E-cadherin independent of beta-catenin/Tcf-mediated Wnt signaling. Oncogene. 26:2290–2298.
  • Hikasa H, Sokol SY. 2011. Phosphorylation of TCF proteins by homeodomain-interacting protein kinase 2. J Biol Chem. 286:12093–12100.
  • Hikasa H, Ezan J, Itoh K, Li X, Klymkowsky MW, Sokol SY. 2010. Regulation of TCF3 by Wnt-dependent phosphorylation during vertebrate axis specification. Dev Cell. 19:521–532.
  • Hino S, Tanji C, Nakayama KI, Kikuchi A. 2005. Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination. Mol Cell Biol. 25:9063–9072.
  • Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y. 2004. The Wnt/B-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development. 131:2791–2801.
  • Hirata H, Hinoda Y, Nakajima K, Kawamoto K, Kikuno N, Kawakami K, Yamamura S, Ueno K, Majid S, Saini S, Ishii N, Dahiya R. 2009. Wnt antagonist gene DKK2 is epigenetically silenced and inhibits renal cancer progression through apoptotic and cell cycle pathways. Clin Cancer Res. 15:5678–5687.
  • Hoverter NP, Waterman ML. 2008. A Wnt-fall for gene regulation: Repression. Sci Signal. 1:pe43.
  • Hsieh JC, Rattner A, Smallwood PM, Nathans J. 1999. Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc Natl Acad Sci USA. 96:3546–3551.
  • Hsu W, Zeng L, Costantini F. 1999. Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 274:3439–3445.
  • Hu T, Li C, Cao Z, Van Raay TJ, Smith JG, Willert K, Solnica-Krezel L, Coffey RJ. 2010. Myristoylated Naked2 antagonizes Wnt-beta-catenin activity by degrading Dishevelled-1 at the plasma membrane. J Biol Chem. 285:13561–13568.
  • Huang H, Mahler-Araujo BM, Sankila A, Chimelli L, Yonekawa Y, Kleihues P, Ohgaki H. 2000. APC mutations in sporadic medulloblastomas. Am J Pathol. 156:433–437.
  • Huang S-MA, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, Finan PM, Tallarico JA, Bouwmeester T, Porter JA, Bauer A, Cong F. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009a; 461:614–620.
  • Huang X, Langelotz C, Hetfeld-Pechoc BK, Schwenk W, Dubiel W. The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. J Mol Biol. 2009b; 391:691–702.
  • Huber AH, Weis WI. 2001. The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin. Cell. 105:391–402.
  • Huber AH, Nelson WJ, Weis WI. 1997. Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell. 90:871–882.
  • Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R, Jaffee E, Ryu B, Jones J, Eshleman JR, Yeo CJ, Cameron JL, Kern SE, Hruban RH, Brown PO, Goggins M. 2003. Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays. Am J Pathol. 162:1151–1162.
  • Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. 1998. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3[beta] and [beta]-catenin and promotes GSK-3[beta]-dependent phosphorylation of [beta]-catenin. EMBO J. 17:1371–1384.
  • Ishitani T, Ninomiya-Tsuji J, Nagai S, Nishita M, Meneghini M, Barker N, Waterman M, Bowerman B, Clevers H, Shibuya H, Matsumoto K. 1999. The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature. 399:798–802.
  • Ishitani T, Ninomiya-Tsuji J, Matsumoto K. 2003. Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling. Mol Cell Biol. 23:1379–1389.
  • Itoh K, Krupnik VE, Sokol SY. 1998. Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and [beta]-catenin. Curr Biol. 8:591–594.
  • Itoh K, Jenny A, Mlodzik M, Sokol SY. 2009. Centrosomal localization of Diversin and its relevance to Wnt signaling. J Cell Sci. 122:3791–3798.
  • Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, Gotlib J, Li K, Manz MG, Keating A, Sawyers CL, Weissman IL. 2004. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 351:657–667.
  • Jamora C, DasGupta R, Kocieniewski P, Fuchs E. 2003. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 422:317–322.
  • Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC. 2012. Structural basis of Wnt recognition by Frizzled. Science. 337:59–64.
  • Jeong WJ, Yoon J, Park JC, Lee SH, Kaduwal S, Kim H, Yoon JB, Choi KY. 2012. Ras stabilization through aberrant activation of Wnt/beta-catenin signaling promotes intestinal tumorigenesis. Sci Signal. 5:ra30.
  • Jernigan KK, Cselenyi CS, Thorne CA, Hanson AJ, Tahinci E, Hajicek N, Oldham WM, Lee LA, Hamm HE, Hepler JR, Kozasa T, Linder ME, Lee E. 2010. Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Science Signal. 3:ra37.
  • Jiang J, Struhl G. 1998. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Nature. 391:493–496.
  • Jin EJ, Erickson CA, Takada S, Burrus LW. 2001. Wnt and BMP signaling govern lineage segregation of melanocytes in the avian embryo. Dev Biol. 233:22–37.
  • Kadowaki T, Wilder E, Klingensmith J, Zachary K, Perrimon N. 1996. The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing. Genes Dev. 10:3116–3128.
  • Kahler RA, Westendorf JJ. 2003. Lymphoid enhancer factor-1 and beta-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J Biol Chem. 278:11937–11944.
  • Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH. 2002. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: Implications for beta-catenin activation in tumorigenesis. Cell. 110:751–762.
  • Katanaev VL, Ponzielli R, Semeriva M, Tomlinson A. 2005. Trimeric G protein-dependent frizzled signaling in Drosophila. Cell. 120:111–122.
  • Kawakami K, Hirata H, Yamamura S, Kikuno N, Saini S, Majid S, Tanaka Y, Kawamoto K, Enokida H, Nakagawa M, Dahiya R. 2009. Functional significance of Wnt inhibitory factor-1 gene in kidney cancer. Cancer Res. 69:8603–8610.
  • Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W. 2004. R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell. 7:525–534.
  • Khan NI, Bradstock KF, Bendall LJ. Activation of Wnt/beta-catenin pathway mediates growth and survival in B-cell progenitor acute lymphoblastic leukaemia. Br J Haematol. 2007a; 138:338–348.
  • Khan Z, Vijayakumar S, de la Torre TV, Rotolo S, Bafico A. Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor. Mol Cell Biol. 2007b; 27:7291–7301.
  • Khramtsov AI, Khramtsova GF, Tretiakova M, Huo D, Olopade OI, Goss KH. 2010. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am J Pathol. 176:2911–2920.
  • Kiecker C, Niehrs C. 2001. A morphogen gradient of Wnt/beta-catenin signalling regulates anteroposterior neural patterning in Xenopus. Development. 128:4189–4201.
  • Killick R, Pollard CC, Asuni AA, Mudher AK, Richardson JC, Rupniak HT, Sheppard PW, Varndell IM, Brion JP, Levey AI, Levy OA, Vestling M, Cowburn R, Lovestone S, Anderton BH. 2001. Presenilin 1 independently regulates beta-catenin stability and transcriptional activity. J Biol Chem. 276:48554–48561.
  • Kim S, Jho E-h. 2010. The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad ubiquitination regulatory factor 2 (Smurf2). J Biol Chem. 285:36420–36426.
  • Kim YS, Kang YK, Kim JB, Han SA, Kim KI, Paik SR. 2000. Beta-catenin expression and mutational analysis in renal cell carcinomas. Pathol Int. 50:725–730.
  • Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. 2005. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 309:1256–1259.
  • Kim K-A, Zhao J, Andarmani S, Kakitani M, Oshima T, Binnerts ME, Abo A, Tomizuka K, Funk WD. 2006. R-Spondin proteins: A novel link to beta-catenin activation. Cell Cycle. 5:23–26.
  • Kim MJ, Chia IV, Costantini F. 2008. SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability. FASEB J. 22:3785–3794.
  • Kimelman D, Xu W. 2006. Beta-catenin destruction complex: Insights and questions from a structural perspective. Oncogene. 25:7482–7491.
  • Kinzler KW, Vogelstein B. 1996. Lessons from hereditary colorectal cancer. Cell. 87:159–170.
  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Boguski MS, Altschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y. 1991. Identification of FAP locus genes from chromosome 5q21. Science. 253:661–665.
  • Kirkpatrick CA, Dimitroff BD, Rawson JM, Selleck SB. 2004. Spatial regulation of Wingless morphogen distribution and signaling by Dally-like protein. Dev Cell. 7:513–523.
  • Kishida M, Hino S, Michiue T, Yamamoto H, Kishida S, Fukui A, Asashima M, Kikuchi A. 2001. Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iepsilon. J Biol Chem. 276:33147–33155.
  • Kitagawa M, Hatakeyama S, Shirane M, Matsumoto M, Ishida N, Hattori K, Nakamichi I, Kikuchi A, Nakayama K. 1999. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 18:2401–2410.
  • Klaus A, Birchmeier W. 2008. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 8:387–398.
  • Kléber M, Sommer L. 2004. Wnt signaling and the regulation of stem cell function. Curr Opin Cell Biol. 16:681–687.
  • Klingensmith J, Nusse R, Perrimon N. 1994. The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. Genes Dev. 8:118–130.
  • Knippschild U, Gocht A, Wolff S, Huber N, Lohler J, Stoter M. 2005. The casein kinase 1 family: Participation in multiple cellular processes in eukaryotes. Cell Signal. 17:675–689.
  • Koch A, Waha A, Tonn JC, Sörensen N, Berthold F, Wolter M, Reifenberger J, Hartmann W, Friedl W, Reifenberger G, Wiestler OD, Pietsch T. 2001. Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Int J Cancer. 93:445–449.
  • Kofron M, Birsoy B, Houston D, Tao Q, Wylie C, Heasman J. 2007. Wnt11/beta-catenin signaling in both oocytes and early embryos acts through LRP6-mediated regulation of axin. Development. 134:503–513.
  • Komekado H, Yamamoto H, Chiba T, Kikuchi A. Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a. Genes Cells. 2007a; 12:521–534.
  • Komekado H, Yamamoto H, Chiba T, Kikuchi A. Glycosylation and palmitoylation of Wnt-3a are coupled to produce an active form of Wnt-3a. Genes Cells. 2007b; 12:521–534.
  • Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, Clevers H. 2012. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 488:665–669.
  • Korinek V, Barker N, Moerer P, Van Donselaar E, Huls G, Peters PJ, Clevers H, others. 1998. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat genet. 19:379–383.
  • Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, Budnik V. 2009. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell. 139:393–404.
  • Kreuger J, Perez L, Giraldez AJ, Cohen SM. 2004. Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity. Dev Cell. 7:503–512.
  • Krieghoff E, Behrens J, Mayr B. 2006. Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention. J Cell Sci. 119:1453–1463.
  • Kuphal F, Behrens J. 2006. E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts. Exp Cell Res. 312:457–467.
  • Kurayoshi M, Yamamoto H, Izumi S, Kikuchi A. 2007. Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling. Biochem J. 402:515–523.
  • Kutay U, Izaurralde E, Bischoff FR, Mattaj IW, Gorlich D. 1997. Dominant-negative mutants of importin-beta block multiple pathways of import and export through the nuclear pore complex. EMBO J. 16:1153–1163.
  • Lagna G, Carnevali F, Marchioni M, Hemmati-Brivanlou A. 1999. Negative regulation of axis formation and Wnt signaling in Xenopus embryos by the F-box/WD40 protein beta TrCP. Mech Dev. 80:101–106.
  • Lai SL, Chien AJ, Moon RT. 2009. Wnt/Fz signaling and the cytoskeleton: Potential roles in tumorigenesis. Cell Res. 19:532–545.
  • Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, Pirinen S, Nieminen P. 2004. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet. 74:1043–1050.
  • Laurent-Puig P, Legoix P, Bluteau O, Belghiti J, Franco D, Binot F, Monges G, Thomas G, Bioulac-Sage P, Zucman-Rossi J. 2001. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology. 120:1763–1773.
  • Lee E, Salic A, Kirschner MW. 2001. Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon. J Cell Biol. 154:983–993.
  • Lee E, Salic A, Krüger R, Heinrich R, Kirschner MW. 2003. The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol. 1:E10.
  • Lee WC, Beebe K, Sudmeier L, Micchelli CA. 2009. Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation. Development. 136:2255–2264.
  • Li W, Ding S. 2010. Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci. 31:36–45.
  • Li X, Yost HJ, Virshup DM, Seeling JM. 2001. Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 20:4122–4131.
  • Li J, Kleeff J, Abiatari I, Kayed H, Giese NA, Felix K, Giese T, Büchler MW, Friess H. 2005. Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer. Mol Cancer. 4:14.
  • Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR, Gerlach JP, Mohammed S, Heck AJ, Maurice MM, Mahmoudi T, Clevers H. 2012. Wnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell. 149:1245–1256.
  • Lin X. 2004. Functions of heparan sulfate proteoglycans in cell signaling during development. Development. 131:6009–6021.
  • Lin X, Perrimon N. 1999. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature. 400:281–284.
  • Lin SY, Xia W, Wang JC, Kwong KY, Spohn B, Wen Y, Pestell RG, Hung MC. 2000. Beta-catenin, a novel prognostic marker for breast cancer: Its roles in cyclin D1 expression and cancer progression. Proc Natl Acad Sci USA. 97:4262–4266.
  • Lin G, Xu N, Xi R. 2008. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature. 455:1119–1123.
  • Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, He X. 1999. Beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci USA. 96:6273–6278.
  • Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, Halling KC, Cunningham JM, Boardman LA, Qian C, Christensen E, Schmidt SS, Roche PC, Smith DI, Thibodeau SN. 2000. Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. Nat Genet. 26:146–147.
  • Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. 2002. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 108:837–847.
  • Liu X, Rubin JS, Kimmel AR. 2005. Rapid, Wnt-induced changes in GSK3β associations that regulate β-catenin stabilization are mediated by Gα proteins. Curr Biol. 15:1989–1997.
  • Liu CC, Prior J, Piwnica-Worms D, Bu G. 2010. LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy. Proc Natl Acad Sci USA. 107:5136–5141.
  • Lo MC, Gay F, Odom R, Shi Y, Lin R. 2004. Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans. Cell. 117:95–106.
  • Logan CY, Nusse R. 2004. The Wnt signaling pathway in development and disease. Ann Rev Cell Dev Biol. 20:781–810.
  • Lowy AM, Fenoglio-Preiser C, Kim OJ, Kordich J, Gomez A, Knight J, James L, Groden J. 2003. Dysregulation of beta-catenin expression correlates with tumor differentiation in pancreatic duct adenocarcinoma. Ann Surg Oncol. 10:284–290.
  • Lui TTH, Lacroix C, Ahmed SM, Goldenberg SJ, Leach CA, Daulat AM, Angers S. 2011. The ubiquitin-specific protease USP34 regulates Axin stability and Wnt/β-catenin signaling. Mol Cell Biol. 31:2053–2065.
  • Lum L, Yao S, Mozer B, Rovescalli A, Von Kessler D, Nirenberg M, Beachy PA. 2003. Identification of Hedgehog pathway components by RNAi in Drosophila cultured cells. Science. 299:2039–2045.
  • Luo W, Peterson A, Garcia BA, Coombs G, Kofahl B, Heinrich R, Shabanowitz J, Hunt DF, Yost HJ, Virshup DM. 2007. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. EMBO J. 26:1511–1521.
  • MacDonald BT, Yokota C, Tamai K, Zeng X, He X. 2008. Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6. J Biol Chem. 283:16115–16123.
  • MacDonald BT, Tamai K, He X. 2009. Wnt/β-catenin signaling: Components, mechanisms, and diseases. Dev Cell. 17:9–26.
  • Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, Biechele TL, Gingras AC, Zheng N, Maccoss MJ, Angers S, Moon RT. 2007. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science. 316:1043–1046.
  • Malik HS, Eickbush TH, Goldfarb DS. 1997. Evolutionary specialization of the nuclear targeting apparatus. Proc Natl Acad Sci USA. 94:13738–13742.
  • Mao J, Wang J, Liu B, Pan W, Farr GHIII, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D. 2001. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 7:801–809.
  • Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C. 2002. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature. 417:664–667.
  • Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis NK. 2002. A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 21:1948–1956.
  • Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P. 2005. ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Proc Natl Acad Sci USA. 102:9182–9187.
  • Marikawa Y, Elinson RP. 1998. Beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos. Mech Dev. 77:75–80.
  • Markowitz SD, Bertagnolli MM. 2009. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 361:2449–2460.
  • Marson A, Foreman R, Chevalier B, Bilodeau S, Kahn M, Young RA, Jaenisch R. 2008. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell. 3:132–135.
  • Mason JO, Kitajewski J, Varmus HE. 1992. Mutational analysis of mouse Wnt-1 identifies two temperature-sensitive alleles and attributes of Wnt-1 protein essential for transformation of a mammary cell line. Mol Biol Cell. 3:521–533.
  • Matsumine A, Ogai A, Senda T, Okumura N, Satoh K, Baeg GH, Kawahara T, Kobayashi S, Okada M, Toyoshima K, Akiyama T. 1996. Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein. Science. 272:1020–1023.
  • Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, Reguart N, Rosell R, McCormick F, Jablons DM. 2004. Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res. 64:4717–4720.
  • McCartney BM, Dierick HA, Kirkpatrick C, Moline MM, Baas A, Peifer M, Bejsovec A. 1999. Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis. J Cell Biol. 146:1303–1318.
  • McCrea PD, Turck CW, Gumbiner B. 1991. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 254:1359–1361.
  • McMahon AP, Moon RT. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell. 1989a; 58:1075–1084.
  • McMahon AP, Moon RT. int-1—A proto-oncogene involved in cell signalling. Development. 1989b; 107 suppl.: 161–167.
  • McManus EJ, Sakamoto K, Armit LJ, Ronaldson L, Shpiro N, Marquez R, Alessi DR. 2005. Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis. EMBO J. 24:1571–1583.
  • Mendoza-Topaz C, Mieszczanek J, Bienz M. 2011. The adenomatous polyposis coli tumour suppressor is essential for Axin complex assembly and function and opposes Axin's interaction with Dishevelled. Open Biol. 1:110013.
  • Mi K, Johnson GVW. 2005. Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway. J Cell Biochem. 95:328–338.
  • Miyazaki K, Fujita T, Ozaki T, Kato C, Kurose Y, Sakamoto M, Kato S, Goto T, Itoyama Y, Aoki M, Nakagawara A. 2004. NEDL1, a novel ubiquitin-protein isopeptide ligase for dishevelled-1, targets mutant superoxide dismutase-1. J Biol Chem. 279:11327–11335.
  • Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destree O, Clevers H. 1996. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 86:391–399.
  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW. 1997. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 275:1787–1790.
  • Mosimann C, Hausmann G, Basler K. 2009. Beta-catenin hits chromatin: Regulation of Wnt target gene activation. Nat Rev Mol Cell Biol. 10:276–286.
  • Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S. 2002. Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev. 16:548–553.
  • Nam J-S, Turcotte TJ, Smith PF, Choi S, Yoon JK. 2006. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 281:13247–13257.
  • Nathke I. 2006. Cytoskeleton out of the cupboard: Colon cancer and cytoskeletal changes induced by loss of APC. Nat Rev Cancer. 6:967–974.
  • Nathke IS, Adams CL, Polakis P, Sellin JH, Nelson WJ. 1996. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol. 134:165–179.
  • Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M, Rosen SD. 2007. Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS One. 2:e392.
  • Nguyen DX, Chiang AC, Zhang XH, Kim JY, Kris MG, Ladanyi M, Gerald WL, Massague J. 2009. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell. 138:51–62.
  • Niemann S, Zhao C, Pascu F, Stahl U, Aulepp U, Niswander L, Weber JL, Muller U. 2004. Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. Am J Hum Genet. 74:558–563.
  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P. 1991. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 253:665–669.
  • Nusse R. 2008. Wnt signaling and stem cell control. Cell Res. 18:523–527.
  • Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H. 1984. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 307:131–136.
  • Nusse R, Brown A, Papkoff J, Scambler P, Shackleford G, McMahon A, Moon R, Varmus H. 1991. A new nomenclature for int-1 and related genes: The Wnt gene family. Cell. 64:231.
  • Nusslein-Volhard C, Wieschaus E. 1980. Mutations affecting segment number and polarity in Drosophila. Nature. 287:795–801.
  • Ohgaki H, Kros JM, Okamoto Y, Gaspert A, Huang H, Kurrer MO, mutations APC. 2004. are infrequent but present in human lung cancer. Cancer Lett. 207:197–203.
  • Ohkawara B, Yamamoto TS, Tada M, Ueno N. 2003. Role of glypican 4 in the regulation of convergent extension movements during gastrulation in Xenopus laevis. Development. 130:2129–2138.
  • Okita K, Yamanaka S. 2010. Induction of pluripotency by defined factors. Exp Cell Res. 316:2565–2570.
  • Orsulic S, Peifer M. 1996. An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. J Cell Biol. 134:1283–1300.
  • Pan W, Choi S-C, Wang H, Qin Y, Volpicelli-Daley L, Swan L, Lucast L, Khoo C, Zhang X, Li L, Abrams CS, Sokol SY, Wu D. 2008. Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science. 321:1350–1353.
  • Panakova D, Sprong H, Marois E, Thiele C, Eaton S. 2005. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature. 435:58–65.
  • Parker DS, Jemison J, Cadigan KM. 2002. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development. 129:2565–2576.
  • Pasca di Magliano M, Biankin AV, Heiser PW, Cano DA, Gutierrez PJA, Deramaudt T, Segara D, Dawson AC, Kench JG, Henshall SM, Sutherland RL, Dlugosz A, Rustgi AK, Hebrok M. 2007. Common activation of canonical Wnt signaling in pancreatic adenocarcinoma. PLoS One. 2:e1155.
  • Peifer M, Polakis P. 2000. Wnt signaling in oncogenesis and embryogenesis—a look outside the nucleus. Science. 287:1606–1609.
  • Peifer M, Pai LM, Casey M. 1994. Phosphorylation of the Drosophila adherens junction protein Armadillo: Roles for wingless signal and zeste-white 3 kinase. Dev Biol. 166:543–556.
  • Pereira L, Yi F, Merrill BJ. 2006. Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal. Mol Cell Biol. 26:7479–7491.
  • Peters JM, McKay RM, McKay JP, Graff JM. 1999. Casein kinase I transduces Wnt signals. Nature. 401:345–350.
  • Peterson-Nedry W, Erdeniz N, Kremer S, Yu J, Baig-Lewis S, Wehrli M. 2008. Unexpectedly robust assembly of the Axin destruction complex regulates Wnt/Wg signaling in Drosophila as revealed by analysis in vivo. Dev Biol. 320:226–241.
  • Pfeiffer S, Ricardo S, Manneville JB, Alexandre C, Vincent JP. 2002. Producing cells retain and recycle Wingless in Drosophila embryos. Curr Biol. 12:957–962.
  • Phillips BT, Kimble J. 2009. A new look at TCF and beta-catenin through the lens of a divergent C. elegans Wnt pathway. Dev Cell. 17:27–34.
  • Piao S, Lee S-H, Kim H, Yum S, Stamos JL, Xu Y, Lee S-J, Lee J, Oh S, Han J-K, Park B-J, Weis WI, Ha N-C. 2008. Direct inhibition of GSK3β by the phosphorylated cytoplasmic domain of LRP6 in Wnt/β-catenin signaling. PLoS One. 3:e4046.
  • Piepenburg O, Vorbruggen G, Jackle H. 2000. Drosophila segment borders result from unilateral repression of hedgehog activity by wingless signaling. Mol Cell. 6:203–209.
  • Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC. 2000. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 407:535–538.
  • Polakis P. 1995. Mutations in the APC gene and their implications for protein structure and function. Curr Opin Genet Dev. 5:66–71.
  • Polakis P. 2000. Wnt signaling and cancer. Genes Dev. 14:1837–1851.
  • Polesskaya A, Seale P, Rudnicki MA. 2003. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell. 113:841–852.
  • Port F, Basler K. 2010. Wnt trafficking: New insights into Wnt maturation, secretion and spreading. Traffic. 11:1265–1271.
  • Port F, Hausmann G, Basler K. 2011. A genome-wide RNA interference screen uncovers two p24 proteins as regulators of Wingless secretion. EMBO Rep. 12:1144–1152.
  • Port F, Kuster M, Herr P, Furger E, Banziger C, Hausmann G, Basler K. 2008. Wingless secretion promotes and requires retromer-dependent cycling of Wntless. Nat Cell Biol. 10:178–185.
  • Price MA. 2006. CKI, there's more than one: Casein kinase I family members in Wnt and Hedgehog signaling. Genes Dev. 20:399–410.
  • Qian C-N, Knol J, Igarashi P, Lin F, Zylstra U, Teh BT, Williams BO. 2005. Cystic renal neoplasia following conditional inactivation of apc in mouse renal tubular epithelium. J Biol Chem. 280:3938–3945.
  • Ratcliffe MJ, Itoh K, Sokol SY. 2000. A positive role for the PP2A catalytic subunit in Wnt signal transduction. J Biol Chem. 275:35680–35683.
  • Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P. 2005. ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J. 24:742–752.
  • Reya T, Clevers H. 2005. Wnt signalling in stem cells and cancer. Nature. 434:843–850.
  • Riggleman B, Wieschaus E, Schedl P. 1989. Molecular analysis of the armadillo locus: Uniformly distributed transcripts and a protein with novel internal repeats are associated with a Drosophila segment polarity gene. Genes Dev. 3:96–113.
  • Riggleman B, Schedl P, Wieschaus E. 1990. Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell. 63:549–560.
  • Rothbacher U, Laurent MN, Deardorff MA, Klein PS, Cho KW, Fraser SE. 2000. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J. 19:1010–1022.
  • Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain SH, Masiarz FR, Munemitsu S, Polakis P. 1993. Association of the APC gene product with beta-catenin. Science. 262:1731–1734.
  • Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P. 1996. Binding of GSK3β to the APC-β-catenin complex and regulation of complex assembly. Science. 272:1023–1026.
  • Rubinfeld B, Tice DA, Polakis P. 2001. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon. J Biol Chem. 276:39037–39045.
  • Ruteshouser EC, Robinson SM, Huff V. 2008. Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes Cancer. 47:461–470.
  • Saadi-Kheddouci S, Berrebi D, Romagnolo B, Cluzeaud F, Peuchmaur M, Kahn A, Vandewalle A, Perret C. 2001. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene. Oncogene. 20:5972–5981.
  • Sadot E, Simcha I, Shtutman M, Ben-Ze'ev A, Geiger B. 1998. Inhibition of beta-catenin-mediated transactivation by cadherin derivatives. Proc Natl Acad Sci USA. 95:15339–15344.
  • Sakanaka C, Leong P, Xu L, Harrison SD, Williams LT. 1999. Casein kinase iepsilon in the wnt pathway: Regulation of beta-catenin function. Proc Natl Acad Sci USA. 96:12548–12552.
  • Sakane H, Yamamoto H, Matsumoto S, Sato A, Kikuchi A. 2012. Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling. J Cell Sci. 125:449–460.
  • Salic A, Lee E, Mayer L, Kirschner MW. 2000. Control of beta-catenin stability: Reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts. Mol Cell. 5:523–532.
  • Samoilov M, Plyasunov S, Arkin AP. 2005. Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations. Proc Natl Acad Sci USA. 102:2310–2315.
  • Sampedro J, Johnston P, Lawrence PA. 1993. A role for wingless in the segmental gradient of Drosophila?. Development. 117:677–687.
  • Sansom OJ, Griffiths DFR, Reed KR, Winton DJ, Clarke AR. 2005. Apc deficiency predisposes to renal carcinoma in the mouse. Oncogene. 24:8205–8210.
  • Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos D, Clevers H, Clarke AR. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature. 446:676–679.
  • Sanson B, White P, Vincent JP. 1996. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature. 383:627–630.
  • Sanson B, Alexandre C, Fascetti N, Vincent JP. 1999. Engrailed and hedgehog make the range of Wingless asymmetric in Drosophila embryos. Cell. 98:207–216.
  • Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. 2004. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med. 10:55–63.
  • Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y, Nakamura Y. 2000. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat Genet. 24:245–250.
  • Schwab KR, Patterson LT, Hartman HA, Song N, Lang RA, Lin X, Potter SS. 2007. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol. 5:15.
  • Schwarz-Romond T, Asbrand C, Bakkers J, Kuhl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W. 2002. The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev. 16:2073–2084.
  • Schwarz-Romond T, Fiedler M, Shibata N, Butler PJ, Kikuchi A, Higuchi Y, Bienz M. The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization. Nat Struct Mol Biol. 2007a; 14:484–492.
  • Schwarz-Romond T, Metcalfe C, Bienz M. Dynamic recruitment of axin by Dishevelled protein assemblies. J Cell Sci. 2007b; 120:2402–2412.
  • Seeling JM, Miller JR, Gil R, Moon RT, White R, Virshup DM. 1999. Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A. Science. 283:2089–2091.
  • Segditsas S, Tomlinson I. 2006. Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene. 25:7531–7537.
  • Semenov MV, Snyder M. 1997. Human dishevelled genes constitute a DHR-containing multigene family. Genomics. 42:302–310.
  • Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. 2001. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 11:951–961.
  • Serban G, Kouchi Z, Baki L, Georgakopoulos A, Litterst CM, Shioi J, Robakis NK. 2005. Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability. J Biol Chem. 280:36007–36012.
  • Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, Chaudhuri S, Guan Y, Janakiraman V, Jaiswal BS, Guillory J, Ha C, Dijkgraaf GJ, Stinson J, Gnad F, Huntley MA, Degenhardt JD, Haverty PM, Bourgon R, Wang W, Koeppen H, Gentleman R, Starr TK, Zhang Z, Largaespada DA, Wu TD, de Sauvage FJ. 2012. Recurrent R-spondin fusions in colon cancer. Nature. 488:660–664.
  • Sharma RP, Chopra VL. 1976. Effect of the Wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev Biol. 48:461–465.
  • Sharma M, Jamieson C, Johnson M, Molloy MP, Henderson BR. 2011. Specific armadillo repeat sequences facilitate beta-catenin nuclear transport in live cells via direct binding to nucleoporins Nup62, Nup153, and RanBP2/Nup358. J Biol Chem. 287:819–831.
  • Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R, Ben-Ze'ev A. 1999. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 96:5522–5527.
  • Siegfried E, Chou TB, Perrimon N. 1992. Wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Cell. 71:1167–1179.
  • Sierra J, Yoshida T, Joazeiro CA, Jones KA. 2006. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 20:586–600.
  • Simons M, Mlodzik M. 2008. Planar cell polarity signaling: From fly development to human disease. Annu Rev Genet. 42:517–540.
  • Sinenko SA, Mandal L, Martinez-Agosto JA, Banerjee U. 2009. Dual role of wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila. Dev Cell. 16:756–763.
  • Smit L, Baas A, Kuipers J, Korswagen H, van de Wetering M, Clevers H. 2004. Wnt activates the Tak1/Nemo-like kinase pathway. J Biol Chem. 279:17232–17240.
  • Smith WC, Harland RM. 1991. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center. Cell. 67:753–765.
  • Smith AG, Heath JK, Donaldson DD, Wong GG, Moreau J, Stahl M, Rogers D. 1988. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature. 336:688–690.
  • Smolich BD, McMahon JA, McMahon AP, Papkoff J. 1993. Wnt family proteins are secreted and associated with the cell surface. Mol Biol Cell. 4:1267–1275.
  • Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftgard R, Clevers H. 2010. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 327:1385–1389.
  • Sobrado P, Jedlicki A, Bustos VH, Allende CC, Allende JE. 2005. Basic region of residues 228-231 of protein kinase CK1alpha is involved in its interaction with axin: Binding to axin does not affect the kinase activity. J Cell Biochem. 94:217–224.
  • Sokol S, Christian JL, Moon RT, Melton DA. 1991. Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell. 67:741–752.
  • Sokol SY, Klingensmith J, Perrimon N, Itoh K. 1995. Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. Development. 121:1637–1647.
  • Song X, Xie T. 2003. Wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila. Development. 130:3259–3268.
  • Song HH, Shi W, Xiang YY, Filmus J. 2005. The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem. 280:2116–2125.
  • Spemann H, Mangold H. 1938. Uber die Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. W Roux Arch Entw Mech Org. 100:599–638.
  • Spink KE, Polakis P, Weis WI. 2000. Structural basis of the Axin-adenomatous polyposis coli interaction. EMBO J. 19:2270–2279.
  • Stockinger A, Eger A, Wolf J, Beug H, Foisner R. 2001. E-cadherin regulates cell growth by modulating proliferation-dependent beta-catenin transcriptional activity. J Cell Biol. 154:1185–1196.
  • Strand M, Micchelli CA. 2011. Quiescent gastric stem cells maintain the adult Drosophila stomach. Proc Natl Acad Sci USA. 108:17696–17701.
  • Strigini M, Cohen SM. 2000. Wingless gradient formation in the Drosophila wing. Curr Biol. 10:293–300.
  • Strovel ET, Wu D, Sussman DJ. 2000. Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. J Biol Chem. 275:2399–2403.
  • Su LK, Vogelstein B, Kinzler KW. 1993. Association of the APC tumor suppressor protein with catenins. Science. 262:1734–1737.
  • Su L-K, Burrell M, Hill DE, Gyuris J, Brent R, Wiltshire R, Trent J, Vogelstein B, Kinzler KW. 1995. APC binds to the novel protein EB1. Cancer Res. 55:2972–2977.
  • Su AI, Welsh JB, Sapinoso LM, Kern SG, Dimitrov P, Lapp H, Schultz PG, Powell SM, Moskaluk CA, Frierson HFJr., Hampton GM. 2001. Molecular classification of human carcinomas by use of gene expression signatures. Cancer Res. 61:7388–7393.
  • Su Y, Fu C, Ishikawa S, Stella A, Kojima M, Shitoh K, Schreiber EM, Day BW, Liu B, is APC. 2008. essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase. Mol Cell. 32:652–661.
  • Sussman DJ, Klingensmith J, Salinas P, Adams PS, Nusse R, Perrimon N. 1994. Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled. Dev Biol. 166:73–86.
  • Sustmann C, Flach H, Ebert H, Eastman Q, Grosschedl R. 2008. Cell-type-specific function of BCL9 involves a transcriptional activation domain that synergizes with beta-catenin. Mol Cell Biol. 28:3526–3537.
  • Sutherland C, Leighton IA, Cohen P. 1993. Inactivation of glycogen synthase kinase-3 beta by phosphorylation: New kinase connections in insulin and growth-factor signalling. Biochem J. 296 Pt 1: 15–19.
  • Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M, Weijenberg MP, Herman JG, Baylin SB. 2002. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet. 31:141–149.
  • Suzuki H, Toyota M, Caraway H, Gabrielson E, Ohmura T, Fujikane T, Nishikawa N, Sogabe Y, Nojima M, Sonoda T, Mori M, Hirata K, Imai K, Shinomura Y, Baylin SB, Tokino T. 2008. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer. Br J Cancer. 98:1147–1156.
  • Swiatek W, Tsai IC, Klimowski L, Pepler A, Barnette J, Yost HJ, Virshup DM. 2004. Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 279:13011–13017.
  • Taelman VF, Dobrowolski R, Plouhinec J-L, Fuentealba LC, Vorwald PP, Gumper I, Sabatini DD, De Robertis EM. 2010. Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell. 143:1136–1148.
  • Takada R, Satomi Y, Kurata T, Ueno N, Norioka S, Kondoh H, Takao T, Takada S. 2006. Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion. Dev Cell. 11:791–801.
  • Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676.
  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872.
  • Takashima S, Mkrtchyan M, Younossi-Hartenstein A, Merriam JR, Hartenstein V. 2008. The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling. Nature. 454:651–655.
  • Takei Y, Ozawa Y, Sato M, Watanabe A, Tabata T. 2004. Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development. 131:73–82.
  • Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X. 2000. LDL-receptor-related proteins in Wnt signal transduction. Nature. 407:530–535.
  • Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, He X. 2004. A Mechanism for Wnt Coreceptor Activation. Mol Cell. 13:149–156.
  • Tan CW, Gardiner BS, Hirokawa Y, Layton MJ, Smith DW, Burgess AW. 2012. Wnt signalling pathway parameters for mammalian cells. PLoS One. 7:e31882.
  • Tanaka K, Kitagawa Y, Kadowaki T. 2002. Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of Wingless in the endoplasmic reticulum. J Biol Chem. 277:12816–12823.
  • Taniguchi K, Roberts LR, Aderca IN, Dong X, Qian C, Murphy LM, Nagorney DM, Burgart LJ, Roche PC, Smith DI, Ross JA, Liu W. 2002. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene. 21:4863–4871.
  • Tanneberger K, Pfister AS, Brauburger K, Schneikert J, Hadjihannas MV, Kriz V, Schulte G, Bryja V, Behrens J. 2011. Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to LRP6 phosphorylation. EMBO J. 30:1433–1443.
  • Tauriello DV, Haegebarth A, Kuper I, Edelmann MJ, Henraat M, Canninga-van Dijk MR, Kessler BM, Clevers H, Maurice MM. 2010. Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl. Mol Cell. 37:607–619.
  • Tauriello DV, Jordens I, Kirchner K, Slootstra JW, Kruitwagen T, Bouwman BA, Noutsou M, Rudiger SG, Schwamborn K, Schambony A, Maurice MM. 2012. Wnt/beta-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proc Natl Acad Sci USA. 109:E812–E820.
  • Teo JL, Kahn M. 2011. The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators. Adv Drug Deliv Rev. 62:1149–1155.
  • Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RDG. 2007. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature. 448:196–199.
  • Tesche LJ, Gerber DA. 2010. Tissue-derived stem and progenitor cells. Stem Cells Int. 2010:824876.
  • Theil T, Aydin S, Koch S, Grotewold L, Rüther U. 2002. Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon. Development. 129:3045–3054.
  • Theisen H, Syed A, Nguyen BT, Lukacsovich T, Purcell J, Srivastava GP, Iron D, Gaudenz K, Nie Q, Wan FY, Waterman ML, Marsh JL. 2007. Wingless directly represses DPP morphogen expression via an armadillo/TCF/Brinker complex. PLoS One. 2:e142.
  • Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M. 2002. A new nuclear component of the Wnt signalling pathway. Nat Cell Biol. 4:367–373.
  • Thorne CA, Hanson AJ, Schneider J, Tahinci E, Orton D, Cselenyi CS, Jernigan KK, Meyers KC, Hang BI, Waterson AG, Kim K, Melancon B, Ghidu VP, Sulikowski GA, LaFleur B, Salic A, Lee LA, Miller DM, Lee E. 2010. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1?. Nat Chem Biol. 6:829–836.
  • Tolwinski NS, Wieschaus E. 2001. Armadillo nuclear import is regulated by cytoplasmic anchor Axin and nuclear anchor dTCF/Pan. Development. 128:2107–2117.
  • Tolwinski NS, Wehrli M, Rives A, Erdeniz N, DiNardo S, Wieschaus E. 2003. Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell. 4:407–418.
  • Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF. 2004. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 74:721–730.
  • Topczewski J, Sepich DS, Myers DC, Walker C, Amores A, Lele Z, Hammerschmidt M, Postlethwait J, Solnica-Krezel L. 2001. The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension. Dev Cell. 1:251–264.
  • Townsley FM, Cliffe A, Bienz M. 2004. Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function. Nat Cell Biol. 6:626–633.
  • Tran H, Hamada F, Schwarz-Romond T, Bienz M. 2008. Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Genes Dev. 22:528–542.
  • Uematsu K, He B, You L, Xu Z, McCormick F, Jablons DM. 2003. Activation of the Wnt pathway in non small cell lung cancer: Evidence of dishevelled overexpression. Oncogene. 22:7218–7221.
  • Uemura K, Kihara T, Kuzuya A, Okawa K, Nishimoto T, Bito H, Ninomiya H, Sugimoto H, Kinoshita A, Shimohama S. 2006. Activity-dependent regulation of beta-catenin via epsilon-cleavage of N-cadherin. Biochem Biophys Res Commun. 345:951–958.
  • Ugolini F, Charafe-Jauffret E, Bardou VJ, Geneix J, Adélaïde J, Labat-Moleur F, Penault-Llorca F, Longy M, Jacquemier J, Birnbaum D, Pébusque MJ. 2001. WNT pathway mammary carcinogenesis: Loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type. Oncogene. 20:5810–5817.
  • van Amerongen R, Nawijn M, Franca-Koh J, Zevenhoven J, van der Gulden H, Jonkers J, Berns A. 2005. Frat is dispensable for canonical Wnt signaling in mammals. Genes Dev. 19:425–430.
  • van Amerongen R, Mikels A, Nusse R. 2008. Alternative wnt signaling is initiated by distinct receptors. Sci Signal. 1:re9.
  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T, Bejsovec A, Peifer M, Mortin M, Clevers H. 1997. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 88:789–799.
  • van den Heuvel M, Harryman-Samos C, Klingensmith J, Perrimon N, Nusse R. 1993. Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. EMBO J. 12:5293–5302.
  • Van Scoyk M, Randall J, Sergew A, Williams LM, Tennis M, Winn RA. 2008. Wnt signaling pathway and lung disease. Transl Res. 151:175–180.
  • Wang J, Sinha T, Wynshaw-Boris A. 2012. Wnt signaling in mammalian development: Lessons from mouse genetics. Cold Spring Harb Perspect Biol. 4:a007963.
  • Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S. 2000. Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature. 407:527–530.
  • Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X. 2007. R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling. J Biol Chem. 282:15903–15911.
  • Wei W, Li M, Wang J, Nie F, Li L. 2012. The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled protein. Mol Cell Biol. 19:3903–3912.
  • Wiechens N, Heinle K, Englmeier L, Schohl A, Fagotto F. 2004. Nucleo-cytoplasmic shuttling of Axin, a negative regulator of the Wnt-beta-catenin Pathway. J Biol Chem. 279:5263–5267.
  • Willert K, Jones KA. 2006. Wnt signaling: Is the party in the nucleus?. Genes Dev. 20:1394–1404.
  • Willert K, Shibamoto S, Nusse R. 1999. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. Genes Dev. 13:1768–1773.
  • Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR3rd, Nusse R. 2003. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 423:448–452.
  • Williams RL, Hilton DJ, Pease S, Willson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM. 1988. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 336:684–687.
  • Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, Kristiansen G, Hsieh J-C, Hofstaedter F, Hartmann A, Knuechel R, Rosenthal A, Pilarsky C. 2003. WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer. J Pathol. 201:204–212.
  • Wolf J, Palmby TR, Gavard J, Williams BO, Gutkind JS. 2008. Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6. FEBS Lett. 582:255–261.
  • Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J. 2000. Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway. Nat Struct Biol. 7:1178–1184.
  • Wong HC, Bourdelas A, Krauss A, Lee HJ, Shao Y, Wu D, Mlodzik M, Shi DL, Zheng J. 2003. Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Mol Cell. 12:1251–1260.
  • Wray J, Hartmann C. 2012. WNTing embryonic stem cells. Trends Cell Biol. 22:159–168.
  • Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. 2008. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 133:340–353.
  • Wu G, Huang H, Garcia Abreu J, He X. 2009. Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS One. 4:e4926.
  • Xing Y, Clements WK, Kimelman D, Xu W. 2003. Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex. Genes Dev. 17:2753–2764.
  • Xing Y, Clements WK, Le Trong I, Hinds TR, Stenkamp R, Kimelman D, Xu W. 2004. Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function. Mol Cell. 15:523–533.
  • Xing Y, Takemaru K, Liu J, Berndt JD, Zheng JJ, Moon RT, Xu W. 2008. Crystal structure of a full-length beta-catenin. Structure. 16:478–487.
  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004a; 116:883–895.
  • Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004b; 116:883–895.
  • Yamada M, Ohnishi J, Ohkawara B, Iemura S, Satoh K, Hyodo-Miura J, Kawachi K, Natsume T, Shibuya H. 2006. NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF). J Biol Chem. 281:20749–20760.
  • Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A. 1999. Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J Biol Chem. 274:10681–10684.
  • Yamamoto A, Nagano T, Takehara S, Hibi M, Aizawa S. 2005. Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF. Cell. 120:223–235.
  • Yamamoto H, Komekado H, Kikuchi A. 2006. Caveolin is necessary for Wnt-3a-dependent internalization of LRP6 and accumulation of beta-catenin. Dev Cell. 11:213–223.
  • Yan D, Lin X. 2009. Shaping morphogen gradients by proteoglycans. Cold Spring Harb Perspect Biol. 1:a002493.
  • Yan D, Wu Y, Feng Y, Lin SC, Lin X. 2009. The core protein of glypican Dally-like determines its biphasic activity in wingless morphogen signaling. Dev Cell. 17:470–481.
  • Yanagawa S, van Leeuwen F, Wodarz A, Klingensmith J, Nusse R. 1995. The dishevelled protein is modified by wingless signaling in Drosophila. Genes Dev. 9:1087–1097.
  • Yang Y, Lijam N, Sussman DJ, Tsang M. 1996. Genomic organization of mouse Dishevelled genes. Gene. 180:121–123.
  • Yang P-T, Lorenowicz MJ, Silhankova M, Coudreuse DYM, Betist MC, Korswagen HC. 2008. Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells. Dev Cell. 14:140–147.
  • Yi F, Pereira L, Merrill BJ. 2008. Tcf3 functions as a steady-state limiter of transcriptional programs of mouse embryonic stem cell self-renewal. Stem Cells. 26:1951–1960.
  • Yi F, Pereira L, Hoffman JA, Shy BR, Yuen CM, Liu DR, Merrill BJ. 2011. Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nature Cell Biol. 13:762–770.
  • Ying Q-L, Nichols J, Chambers I, Smith A. 2003. BMP Induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell. 115:281–292.
  • Yokoya F, Imamoto N, Tachibana T, Yoneda Y. 1999. Beta-catenin can be transported into the nucleus in a Ran-unassisted manner. Mol Biol Cell. 10:1119–1131.
  • Yokoyama N, Malbon CC. 2007. Phosphoprotein phosphatase-2A docks to Dishevelled and counterregulates Wnt3a/beta-catenin signaling. J Mol Signal. 2:12.
  • Yost C, Torres M, Miller JR, Huang E, Kimelman D, Moon RT. 1996. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev. 10:1443–1454.
  • Yost C, Farr GH3rd, Pierce SB, Ferkey DM, Chen MM, Kimelman D. 1998. GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis. Cell. 93:1031–1041.
  • Yu X, Waltzer L, Bienz M. 1999. A new Drosophila APC homologue associated with adhesive zones of epithelial cells. Nat Cell Biol. 1:144–151.
  • Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL3rd, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F. 1997. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell. 90:181–192.
  • Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005a; 438:873–877.
  • Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature. 2005b; 438:873–877.
  • Zeng G, Germinaro M, Micsenyi A, Monga NK, Bell A, Sood A, Malhotra V, Sood N, Midda V, Monga DK, Kokkinakis DM, Monga SPS. 2006. Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma. Neoplasia. 8:279–289.
  • Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, Almeida K, Wang J, Doble B, Woodgett J, Wynshaw-Boris A, Hsieh J-C, He X. 2008. Initiation of Wnt signaling: Control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions. Development. 135:367–375.
  • Zhang L, Jia J, Wang B, Amanai K, Wharton KAJr., Jiang J. 2006. Regulation of wingless signaling by the CKI family in Drosophila limb development. Dev Biol. 299:221–237.
  • Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, Schirle M, Shi X, Hild M, Bauer A, Myer VE, Finan PM, Porter JA, Huang S-MA, Cong F. 2011. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 13:623–629.
  • Zhang X, Abreu JG, Yokota C, Macdonald BT, Singh S, Coburn KL, Cheong SM, Zhang MM, Ye QZ, Hang HC, Steen H, He X. 2012. Tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation. Cell. 149:1565–1577.
  • Zhao B, Schlesiger C, Masucci MG, Lindsten K. 2009. The ubiquitin specific protease 4 (USP4) is a new player in the Wnt signalling pathway. J Cell Mol Med. 13:1886–1895.

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