Wnt Proteins Induce Dishevelled Phosphorylation via an LRP5/6- Independent Mechanism, Irrespective of Their Ability To Stabilize β-Catenin

REFERENCES

• Adler, P. N. 2002. Planar signaling and morphogenesis in Drosophila. Dev. Cell 2:525–535.
   PubMedGoogle Scholar
• Amit, S., Hatzubai A., Birman Y., Andersen J. S., Ben-Shushan E., Mann M., Ben-Neriah Y., and 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.
   PubMed Web of Science ®Google Scholar
• Axelrod, J. D. 2001. Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev. 15:1182–1187.
   PubMedGoogle Scholar
• Axelrod, J. D., Matsuno K., Artavanis-Tsakonas S., and Perrimon N.. 1996. Interaction between Wingless and Notch signaling pathways mediated by Dishevelled. Science 271:1826–1832.
   PubMed Web of Science ®Google Scholar
• Axelrod, J. D., Miller J. R., Shulman J. M., Moon R. T., and Perrimon N.. 1998. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12:2610–2622.
   PubMed Web of Science ®Google Scholar
• Bafico, A., Liu G., Yaniv A., Gazit A., and Aaronson S. A.. 2001. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat. Cell Biol. 3:683–686.
   PubMed Web of Science ®Google Scholar
• Bessone, S., Vidal F., Le Bouc Y., Epelbaum J., Bluet-Pajot M. T., and Darmon M.. 1999. EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways. Dev Biol. 214:87–101.
   PubMedGoogle Scholar
• Bhanot, P., Brink M., Samos C. H., Hsieh J. C., Wang Y., Macke J. P., Andrew D., Nathans J., and Nusse R.. 1996. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382:225–230.
   PubMed Web of Science ®Google Scholar
• Boutros, M., and Mlodzik M.. 1999. Dishevelled: at the crossroads of divergent intracellular signaling pathways. Mech. Dev. 83:27–37.
   PubMed Web of Science ®Google Scholar
• Boutros, M., Paricio N., Strutt D. I., and Mlodzik M.. 1998. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell 94:109–118.
   PubMed Web of Science ®Google Scholar
• Brennan, K., Gonzalez-Sancho J. M., Castelo-Soccio L. A., Howe L. R., and Brown A. M. C.. Truncated mutants of the putative Wnt receptor LRP6/Arrow can stabilize beta-catenin independently of Frizzled proteins. Oncogene, in press.
   Google Scholar
• Brown, A. M. C. 2001. Wnt signaling in breast cancer: have we come full circle? Breast Cancer Res. 3:351–355.
   PubMedGoogle Scholar
• Brown, A. M. C., Papkoff J., Fung Y. K. T., Shackleford G. M., and Varmus H. E.. 1987. Identification of protein products encoded by the proto-oncogene int-1. Mol. Cell. Biol. 7:3971–3977.
   PubMed Web of Science ®Google Scholar
• Brown, A. M. C., Wildin R. A., Prendergast T. J., and Varmus H. E.. 1986. A retrovirus vector expressing the putative mammary oncogene int-1 causes partial transformation of a mammary epithelial cell line. Cell 46:1001–1009.
   PubMed Web of Science ®Google Scholar
• Brown, S. D., Twells R. C., Hey P. J., Cox R. D., Levy E. R., Soderman A. R., Metzker M. L., Caskey C. T., Todd J. A., and Hess J. F.. 1998. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem. Biophys. Res. Commun. 248:879–888.
   PubMed Web of Science ®Google Scholar
• Cadigan, K. M., and Nusse R.. 1997. Wnt signaling: a common theme in animal development. Genes Dev. 11:3286–3305.
   PubMed Web of Science ®Google Scholar
• Capelluto, D. G., Kutateladze T. G., Habas R., Finkielstein C. V., He X., and Overduin M.. 2002. The DIX domain targets dishevelled to actin stress fibres and vesicular membranes. Nature 419:726–729.
   PubMedGoogle Scholar
• Chan, S. D., Karpf D. B., Fowlkes M. E., Hooks M., Bradley M. S., Vuong V., Bambino T., Liu M. Y., Arnaud C. D., Strewler G. J., et al. 1992. Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues. J. Biol. Chem. 267:25202–25207.
   PubMedGoogle Scholar
• Crnogorac-Jurcevic, T., Efthimiou E., Capelli P., Blaveri E., Baron A., Terris B., Jones M., Tyson K., Bassi C., Scarpa A., and Lemoine N. R.. 2001. Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 20:7437–7446.
   PubMed Web of Science ®Google Scholar
• Dale, T. C. 1998. Signal transduction by the Wnt family of ligands. Biochem. J. 329:209–223.
   PubMed Web of Science ®Google Scholar
• Drewes, G., Ebneth A., Preuss U., Mandelkow E. M., and Mandelkow E.. 1997. MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell 89:297–308.
   PubMed Web of Science ®Google Scholar
• Du, S. J., Purcell S. M., Christian J. L., and Moon R. T.. 1995. Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos. Mol. Cell. Biol. 15:2625–2634.
   PubMedGoogle Scholar
• Eastman, Q., and Grosschedl R.. 1999. Regulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr. Opin. Cell Biol. 11:233–240.
   PubMed Web of Science ®Google Scholar
• Gao, Z. H., Seeling J. M., Hill V., Yochum A., and Virshup D. M.. 2002. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc. Natl. Acad. Sci. USA 99:1182–1187.
   PubMedGoogle Scholar
• Giarre, M., Semenov M. V., and Brown A. M. C.. 1998. Wnt signaling stabilizes the dual function protein beta-catenin in diverse cell types. Ann. N. Y. Acad. Sci. 857:43–55.
   PubMedGoogle Scholar
• Giles, R. H., van Es J. H., and Clevers H.. 2003. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta 1653:1–24.
   PubMed Web of Science ®Google Scholar
• Guo, S., and Kemphues K. J.. 1995. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81:611–620.
   PubMed Web of Science ®Google Scholar
• Hedgepeth, C. M., Conrad L. J., Zhang J., Huang H. C., Lee V. M., and Klein P. S.. 1997. Activation of the Wnt signaling pathway: a molecular mechanism for lithium action. Dev. Biol. 185:82–91.
   PubMed Web of Science ®Google Scholar
• Heisenberg, C. P., Tada M., Rauch G. J., Saude L., Concha M. L., Geisler R., Stemple D. L., Smith J. C., and Wilson S. W.. 2000. Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405:76–81.
   PubMed Web of Science ®Google Scholar
• Hey, P. J., Twells R. C., Phillips M. S., Yusuke N., Brown S. D., Kawaguchi Y., Cox R., Guochun X., Dugan V., Hammond H., Metzker M. L., Todd J. A., and Hess J. F.. 1998. Cloning of a novel member of the low-density lipoprotein receptor family. Gene 216:103–111.
   PubMed Web of Science ®Google Scholar
• Howe, L. R., Crawford H. C., Subbaramaiah K., Hassell J. A., Dannenberg A. J., and Brown A. M. C.. 2001. PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J. Biol. Chem. 276:20108–20115.
   PubMedGoogle Scholar
• Hsieh, J. C., Rattner A., Smallwood P. M., and 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.
   PubMedGoogle Scholar
• Iozzo, R. V., Eichstetter I., and Danielson K. G.. 1995. Aberrant expression of the growth factor Wnt-5a in human malignancy. Cell Regul. 55:3495–3499.
   Google Scholar
• Karasawa, T., Yokokura H., Kitajewski J., and Lombroso P. J.. 2002. Frizzled-9 is activated by Wnt-2 and functions in Wnt/beta-catenin signaling. J. Biol. Chem. 277:37479–37486.
   PubMedGoogle Scholar
• Kilian, B., Mansukoski H., Barbosa F. C., Ulrich F., Tada M., and Heisenberg C. P.. 2003. The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech. Dev. 120:467–476.
   PubMedGoogle Scholar
• Klingensmith, J., Nusse R., and 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.
   PubMedGoogle Scholar
• Korinek, V., Barker N., Morin P. J., van Wichen D., de Weger R., Kinzler K. W., Vogelstein B., and Clevers H.. 1997. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787.
   PubMed Web of Science ®Google Scholar
• Krasnow, R. E., Wong L. L., and Adler P. N.. 1995. Dishevelled is a component of the frizzled signaling pathway in Drosophila. Development 121:4095–4102.
   PubMedGoogle Scholar
• Kuhl, M., Sheldahl L. C., Malbon C. C., and Moon R. T.. 2000. Ca2+/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus. J. Biol. Chem. 275:12701–12711.
   PubMed Web of Science ®Google Scholar
• Kuhl, M., Sheldahl L. C., Park M., Miller J. R., and Moon R. T.. 2000. The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet. 16:279–283.
   PubMed Web of Science ®Google Scholar
• Lee, E., Salic A., and Kirschner M. W.. 2001. Physiological regulation of beta-catenin stability by Tcf3 and CK1epsilon. J. Cell Biol. 154:983–993.
   PubMedGoogle Scholar
• Lee, J. S., Ishimoto A., and Yanagawa S.. 1999. Characterization of mouse dishevelled (Dvl) proteins in Wnt/Wingless signaling pathway. J. Biol. Chem. 274:21464–21470.
   PubMedGoogle Scholar
• Lejeune, S., Huguet E. L., Hamby A., Poulsom R., and Harris A. L.. 1995. Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Clin. Cancer Res. 1:215–222.
   PubMed Web of Science ®Google Scholar
• Leyns, L., Bouwmeester T., Kim S.-H., Piccolo S., and DeRobertis E. M.. 1997. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88:747–756.
   PubMed Web of Science ®Google Scholar
• Li, L., Mao J., Sun L., Liu W., and Wu D.. 2002. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J. Biol. Chem. 277:5977–5981.
   PubMed Web of Science ®Google Scholar
• Li, L., Yuan H., Xie W., Mao J., Caruso A. M., McMahon A., Sussman D. J., and Wu D.. 1999. Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells. J. Biol. Chem. 274:129–134.
   PubMed Web of Science ®Google Scholar
• Liu, C., Li Y., Semenov M., Han C., Baeg G. H., Tan Y., Zhang Z., Lin X., and He X.. 2002. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 108:837–847.
   PubMed Web of Science ®Google Scholar
• Liu, G., Bafico A., Harris V. K., and Aaronson S. A.. 2003. A novel mechanism for Wnt activation of canonical signaling through the LRP6 receptor. Mol. Cell. Biol. 23:5825–5835.
   PubMedGoogle Scholar
• Mao, B., Wu W., Li Y., Hoppe D., Stannek P., Glinka A., and Niehrs C.. 2001. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411:321–325.
   PubMed Web of Science ®Google Scholar
• Mao, J., Wang J., Liu B., Pan W., Farr III G. H., Flynn C., Yuan H., Takada S., Kimelman D., Li L., and 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.
   PubMed Web of Science ®Google Scholar
• McKay, R. M., Peters J. M., and Graff J. M.. 2001. The casein kinase I family in Wnt signaling. Dev. Biol. 235:388–396.
   PubMedGoogle Scholar
• Miller, J. R. 2002. The Wnts. Genome Biol. 3:reviews 3001.1–3001.15.
   Google Scholar
• Mlodzik, M. 2002. Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet. 18:564–571.
   PubMed Web of Science ®Google Scholar
• Moon, R. T., Campbell R. M., Christian J. L., McGrew L. L., Shih J., and Fraser S.. 1993. Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis. Development 119:97–111.
   PubMed Web of Science ®Google Scholar
• Noordermeer, J., Klingensmith J., Perrimon N., and Nusse R.. 1994. Dishevelled and Armadillo act in the Wingless signalling pathway in Drosophila. Nature 367:80–83.
   PubMedGoogle Scholar
• Nusse, R., Samos C. H., Brink M., Willert K., Cadigan K. M., Wodarz A., Fish M., and Rulifson E.. 1997. Cell culture and whole animal approaches to understanding signaling by Wnt proteins in Drosophila. Cold Spring Harbor Symp. Quant. Biol. 62:185–190.
   Google Scholar
• Nusse, R., and Varmus H. E.. 1982. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109.
   PubMed Web of Science ®Google Scholar
• Nusse, R., and Varmus H. E.. 1992. Wnt genes. Cell 69:1073–1087.
   PubMed Web of Science ®Google Scholar
• Pandur, P., Lasche M., Eisenberg L. M., and Kuhl M.. 2002. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418:636–641.
   PubMed Web of Science ®Google Scholar
• Pear, W. S., Nolan G. P., Scott M. L., and Baltimore D.. 1993. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90:8392–8396.
   PubMed Web of Science ®Google Scholar
• Peters, J. M., McKay R. M., McKay J. P., and Graff J. M.. 1999. Casein kinase I transduces Wnt signals. Nature 401:345–350.
   PubMed Web of Science ®Google Scholar
• Polakis, P. 2000. Wnt signaling and cancer. Genes Dev. 14:1837–1851.
   PubMed Web of Science ®Google Scholar
• Rauch, G. J., Hammerschmidt M., Blader P., Schauerte H. E., Strahle U., Ingham P. W., McMahon A. P., and Haffter P.. 1997. Wnt5 is required for tail formation in the zebrafish embryo. Cold Spring Harbor Symp. Quant. Biol. 62:227–234.
   Google Scholar
• Rijsewijk, F., Schuerman M., Wagenaar E., Parren P., Weigel D., and Nusse R.. 1987. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50:649–657.
   PubMed Web of Science ®Google Scholar
• Rothbacher, U., Laurent M. N., Deardorff M. A., Klein P. S., Cho K. W., and Fraser S. E.. 2000. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J. 19:1010–1022.
   PubMed Web of Science ®Google Scholar
• Rubinfeld, B., Tice D. A., and Polakis P.. 2001. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon. J. Biol. Chem. 276:39037–39045.
   PubMed Web of Science ®Google Scholar
• Sakanaka, C., Leong P., Xu L., Harrison S. D., and Williams L. T.. 1999. Casein kinase 1 epsilon in the wnt pathway: regulation of beta-catenin function. Proc. Natl. Acad. Sci. USA 96:12548–12552.
   PubMed Web of Science ®Google Scholar
• Saneyoshi, T., Kume S., Amasaki Y., and Mikoshiba K.. 2002. The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 417:295–299.
   PubMed Web of Science ®Google Scholar
• Schweizer, L., and Varmus H.. 2003. Wnt/Wingless signaling through beta-catenin requires the function of both LRP/Arrow and frizzled classes of receptors. BMC Cell Biol. 4:4.
   PubMed Web of Science ®Google Scholar
• Semenov, M. V., and Snyder M.. 1997. Human dishevelled genes constitute a DHR-containing multigene family. Genomics 42:302–310.
   PubMed Web of Science ®Google Scholar
• Semenov, M. V., Tamai K., Brott B. K., Kuhl M., Sokol S., and He X.. 2001. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr. Biol. 11:951–961.
   PubMed Web of Science ®Google Scholar
• Sheldahl, L. C., Park M., Malbon C. C., and Moon R. T.. 1999. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr. Biol. 9:695–698.
   PubMed Web of Science ®Google Scholar
• Shimizu, H., Julius M. A., Giarre M., Zheng Z., Brown A. M., and Kitajewski J.. 1997. Transformation by Wnt family proteins correlates with regulation of beta-catenin. Cell Growth Differ. 8:1349–1358.
   PubMedGoogle Scholar
• Slusarski, D. C., Corces V. G., and Moon R. T.. 1997. Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature 390:410–413.
   PubMed Web of Science ®Google Scholar
• Smalley, M. J., and Dale T. C.. 1999. Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev. 18:215–230.
   PubMedGoogle Scholar
• Smalley, M. J., Sara E., Paterson H., Naylor S., Cook D., Jayatilake H., Fryer L. G., Hutchinson L., Fry M. J., and Dale T. C.. 1999. Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. EMBO J. 18:2823–2835.
   PubMed Web of Science ®Google Scholar
• Sokol, S., Christian J. L., Moon R. T., and Melton D. A.. 1991. Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell 67:741–752.
   PubMedGoogle Scholar
• Sokol, S. Y. 1996. Analysis of Dishevelled signalling pathways during Xenopus development. Curr. Biol. 6:1456–1467.
   PubMedGoogle Scholar
• Strutt, D., Johnson R., Cooper K., and Bray S.. 2002. Asymmetric localization of frizzled and the determination of notch-dependent cell fate in the Drosophila eye. Curr. Biol. 12:813–824.
   PubMedGoogle Scholar
• Strutt, D. I., Weber U., and Mlokzik M.. 1997. The role of RhoA in tissue polarity and frizzled signaling. Nature 387:292–295.
   PubMedGoogle Scholar
• Sun, T. Q., Lu B., Feng J. J., Reinhard C., Jan Y. N., Fantl W. J., and Williams L. T.. 2001. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat. Cell Biol. 3:628–636.
   PubMedGoogle Scholar
• Sussman, D. J., Klingensmith J., Salinas P., Adams P. S., Nusse R., and Perrimon N.. 1994. Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled. Dev. Biol. 166:73–86.
   PubMedGoogle Scholar
• Tamai, K., Semenov M., Kato Y., Spokony R., Liu C., Katsuyama Y., Hess F., Saint-Jeannet J. P., and He X.. 2000. LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530–535.
   PubMed Web of Science ®Google Scholar
• Tamai, K., Zeng X., Liu C., Zhang X., Harada Y., Chang Z., and He X.. 2004. A mechanism for Wnt coreceptor activation. Mol. Cell 13:149–156.
   PubMed Web of Science ®Google Scholar
• Theisen, H., Purcell J., Bennett M., Kansagara D., Syed A., and Marsh J. L.. 1994. dishevelled is required during wingless signaling to establish both cell polarity and cell identity. Development 120:347–360.
   PubMed Web of Science ®Google Scholar
• Tomlinson, A., Strapps W. R., and Heemskerk J.. 1997. Linking Frizzled and Wnt signaling in Drosophila development. Development 124:4515–4521.
   PubMed Web of Science ®Google Scholar
• Van Leeuwen, F., Samos C. H., and Nusse R.. 1994. Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cells. Nature 368:342–344.
   PubMed Web of Science ®Google Scholar
• Vinson, C. R., Conover S., and Adler P. N.. 1989. A Drosophila tissue polarity locus encodes a protein containing seven potential transmembrane domains. Nature 338:263–264.
   PubMed Web of Science ®Google Scholar
• Wallingford, J. B., Rowning B. A., Vogeli K. M., Rothbacher U., Fraser S. E., and Harland R. M.. 2000. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405:81–85.
   PubMed Web of Science ®Google Scholar
• Wang, S., Krinks M., Lin K., Luyten F. P., and Moos M.. 1997. Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. Cell 88:757–766.
   PubMed Web of Science ®Google Scholar
• Wang, Y., Macke J. P., Abella B. S., Andreasson K., Worley P., Gilbert D. J., Copeland N. G., Jenkins N. A., and Nathans J.. 1996. A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled. J. Biol. Chem. 271:4468–4476.
   PubMed Web of Science ®Google Scholar
• Weeraratna, A. T., Jiang Y., Hostetter G., Rosenblatt K., Duray P., Bittner M., and Trent J. M.. 2002. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1:279–288.
   PubMed Web of Science ®Google Scholar
• Wharton, K. A., Jr. 2003. Runnin' with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction. Dev. Biol. 253:1–17.
   PubMed Web of Science ®Google Scholar
• Willert, K., Brink M., Wodarz A., Varmus H., and Nusse R.. 1997. Casein kinase 2 associates with and phosphorylates dishevelled. EMBO J. 16:3089–3096.
   PubMed Web of Science ®Google Scholar
• Willert, K., Brown J. D., Danenberg E., Duncan A. W., Weissman I. L., Reya T., Yates III J. R., and Nusse R.. 2003. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423:448–452.
   PubMed Web of Science ®Google Scholar
• Willert, K., Shibamoto S., and Nusse R.. 1999. Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex. Genes Dev. 13:1768–1773.
   PubMed Web of Science ®Google Scholar
• Winter, C. G., Wang B., Ballew A., Royou A., Karess R., Axelrod J. D., and Luo L.. 2001. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 105:81–91.
   PubMed Web of Science ®Google Scholar
• Yamaguchi, T. P., Bradley A., McMahon A. P., and Jones S.. 1999. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126:1211–1223.
   PubMed Web of Science ®Google Scholar
• Yamanaka, H., Moriguchi T., Masuyama N., Kusakabe M., Hanafusa H., Takada R., Takada S., and Nishida E.. 2002. JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. EMBO Rep. 3:69–75.
   PubMed Web of Science ®Google Scholar
• Yanagawa, S., Matsuda Y., Lee J. S., Matsubayashi H., Sese S., Kadowaki T., and Ishimoto A.. 2002. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila. EMBO J. 21:1733–1742.
   PubMed Web of Science ®Google Scholar
• Yanagawa, S., Van Leeuwen F., Wodarz A., Klingensmith J., and Nusse R.. 1995. The Dishevelled protein is modified by Wingless signaling in Drosophila. Genes Dev. 9:1087–1097.
   PubMed Web of Science ®Google Scholar
• Yang, Y., Lijam N., Sussman D. J., and Tsang M.. 1996. Genomic organization of mouse Dishevelled genes. Gene 180:121–123.
   PubMedGoogle Scholar
• Zorn, A. M. 2001. Wnt signalling: antagonistic Dickkopfs. Curr. Biol. 11:R592–R595.
   PubMed Web of Science ®Google Scholar