Skip to main content
SpringerLink
Log in
SpringerLink
Log in

β-Catenin-Independent Wnt Pathways: Signals, Core Proteins, and Effectors

  • Protocol
Wnt Signaling

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 468))

Abstract

Wnt signaling activates several distinct intracellular pathways, which are important for cell proliferation, differentiation, and polarity. Wnt proteins are secreted molecules that typically signal across the membrane via interaction with the transmembrane receptor Frizzled. Following interaction with Frizzled, the downstream effect of the most widely studied Wnt pathway is stabilization and nuclear translocation of the cytosolic protein, β-catenin. In this chapter, we discuss two β-catenin-independent branches of Wnt signaling: 1) Wnt/planar cell polarity (PCP), a Wnt pathway that signals through the small GTPases, Rho and Rac, to promote changes in the actin cytoskeleton, and 2) Wnt/Ca2+, a Wnt pathway that promotes intracellular calcium transients and negatively regulates the Wnt/β-catenin pathway. Finally, during the course of our discussion, we highlight areas that require future research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Moon, R.T., A.D. Kohn, G.V. De Ferrari, and A. Kaykas. (2004) WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 5, 691–701.

    Article  CAS  PubMed  Google Scholar 

  2. Seifert, J.R. and M. Mlodzik. (2007) Friz-zled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility. Nat Rev Genet. 8, 126–138.

    Article  CAS  PubMed  Google Scholar 

  3. Wu, J., T.J. Klein, and M. Mlodzik. (2004) Subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity. PLoS Biol. 2, E158.

    Article  PubMed  Google Scholar 

  4. Amonlirdviman, K., N.A. Khare, D.R. Tree, W.S. Chen, J.D. Axelrod, and C.J. Tomlin. (2005) Mathematical modeling of planar cell polarity to understand domineering nonautonomy. Science. 307, 423–426.

    Article  CAS  PubMed  Google Scholar 

  5. Yang, C.H., J.D. Axelrod, and M.A. Simon. (2002) Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye. Cell. 108, 675–688.

    Article  CAS  PubMed  Google Scholar 

  6. Axelrod, J.D. (2001) Unipolar membrane association of Dishevelled mediates Frizzled planar cell polarity signaling. Genes Dev. 15, 1182–1187.

    CAS  PubMed  Google Scholar 

  7. Das, G., A. Jenny, T.J. Klein, S. Eaton, and M. Mlodzik. (2004) Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development. 131, 4467–4476.

    Article  CAS  PubMed  Google Scholar 

  8. Strutt, D.I. (2001) Asymmetric localization of frizzled and the establishment of cell polarity in the Drosophila wing. Mol Cell. 7, 367–375.

    Article  CAS  PubMed  Google Scholar 

  9. Bastock, R., H. Strutt, and D. Strutt. (2003) Strabismus is asymmetrically localised and binds to Prickle and Dishevelled during Drosophila planar polarity patterning. Development. 130, 3007–3014.

    Article  CAS  PubMed  Google Scholar 

  10. Tree, D.R., J.M. Shulman, R. Rousset, M.P. Scott, D. Gubb, and J.D. Axelrod. (2002) Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Cell. 109, 371–381.

    Article  CAS  PubMed  Google Scholar 

  11. Jenny, A., J. Reynolds-Kenneally, G. Das, M. Burnett, and M. Mlodzik. (2005) Diego and Prickle regulate Frizzled planar cell polarity signalling by competing for Dishevelled binding. Nat Cell Biol. 7, 691–697.

    Article  CAS  PubMed  Google Scholar 

  12. Usui, T., Y. Shima, Y. Shimada, S. Hirano, R.W. Burgess, T.L. Schwarz, et al. (1999) Flamingo, a seven-pass transmembrane cad-herin, regulates planar cell polarity under the control of Frizzled. Cell. 98, 585–595.

    Article  CAS  PubMed  Google Scholar 

  13. Adler, P.N., J. Charlton, K.H. Jones, and J. Liu. (1994) The cold-sensitive period for frizzled in the development of wing hair polarity ends prior to the start of hair morphogenesis. Mech Dev. 46, 101–107.

    Article  CAS  PubMed  Google Scholar 

  14. Eaton, S., R. Wepf, and K. Simons. (1996) Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. J Cell Biol. 135, 1277–1289.

    Article  CAS  PubMed  Google Scholar 

  15. Fanto, M., U. Weber, D.I. Strutt, and M. Mlodzik. (2000) Nuclear signaling by Rac and Rho GTPases is required in the establishment of epithelial planar polarity in the Drosophila eye. Curr Biol. 10, 979–988.

    Article  CAS  PubMed  Google Scholar 

  16. Schwarz-Romond, T., C. Asbrand, J. Bakkers, M. Kuhl, H.J. Schaeffer, J. Huelsken, et al. (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.

    Article  CAS  PubMed  Google Scholar 

  17. Park, M. and R.T. Moon. (2002) The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. Nat Cell Biol. 4, 20–25.

    Article  CAS  PubMed  Google Scholar 

  18. Wallingford, J.B., B.A. Rowning, K.M. Vogeli, U. Rothbacher, S.E. Fraser, and R.M. Harland. (2000) Dishevelled controls cell polarity during Xenopus gastrulation. Nature. 405, 81–85.

    Article  CAS  PubMed  Google Scholar 

  19. Wang, J., N.S. Hamblet, S. Mark, M.E. Dickinson, B.C. Brinkman, N. Segil, et al. (2006) Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development. 133, 1767–1778.

    Article  CAS  PubMed  Google Scholar 

  20. Formstone, C.J. and I. Mason. (2005) Combinatorial activity of Flamingo proteins directs convergence and extension within the early zebrafish embryo via the planar cell polarity pathway. Dev Biol. 282, 320–335.

    Article  CAS  PubMed  Google Scholar 

  21. Takeuchi, M., J. Nakabayashi, T. Sakaguchi, T.S. Yamamoto, H. Takahashi, H. Takeda, et al. (2003) The prickle-related gene in vertebrates is essential for gastrulation cell movements. Curr Biol. 13, 674–679.

    Article  CAS  PubMed  Google Scholar 

  22. Veeman, M.T., D.C. Slusarski, A. Kaykas, S.H. Louie, and R.T. Moon. (2003) Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements. Curr Biol. 13, 680–685.

    Article  CAS  PubMed  Google Scholar 

  23. Kilian, B., H. Mansukoski, F.C. Barbosa, F. Ulrich, M. Tada, and C.P. Heisenberg. (2003) The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech Dev. 120, 467–476.

    Article  CAS  PubMed  Google Scholar 

  24. Heisenberg, C.P., M. Tada, G.J. Rauch, L. Saude, M.L. Concha, R. Geisler, et al. (2000) Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature. 405, 76–81.

    Article  CAS  PubMed  Google Scholar 

  25. Carreira-Barbosa, F., M.L. Concha, M. Takeuchi, N. Ueno, S.W. Wilson, and M. Tada. (2003) Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Development. 130, 4037–4046.

    Article  CAS  PubMed  Google Scholar 

  26. Moeller, H., A. Jenny, H.J. Schaeffer, T. Schwarz-Romond, M. Mlodzik, M. Ham-merschmidt, et al. (2006) Diversin regulates heart formation and gastrulation movements in development. Proc Natl Acad Sci U S A. 103, 15900–15905.

    Article  CAS  PubMed  Google Scholar 

  27. Axelrod, J.D., J.R. Miller, J.M. Shulman, R.T. Moon, and N. Perrimon. (1998) Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12, 2610–2622.

    Article  CAS  PubMed  Google Scholar 

  28. Boutros, M., J. Mihaly, T. Bouwmeester, and M. Mlodzik. (2000) Signaling specificity by Frizzled receptors in Drosophila. Science. 288, 1825–1828.

    Article  CAS  PubMed  Google Scholar 

  29. Yanagawa, S., F. van Leeuwen, A. Wodarz, J. Klingensmith, and R. Nusse. (1995) The dishevelled protein is modified by wingless signaling in Drosophila. Genes Dev. 9, 1087–1097.

    Article  CAS  PubMed  Google Scholar 

  30. Gonzalez-Sancho, J.M., K.R. Brennan, L.A. Castelo-Soccio, and A.M. Brown. (2004) Wnt proteins induce dishevelled phosphor-ylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 24, 4757–4768.

    Article  CAS  PubMed  Google Scholar 

  31. Liu, T., A.J. DeCostanzo, X. Liu, H. Wang, S. Hallagan, R.T. Moon, et al. (2001) G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science. 292, 1718–1722.

    Article  CAS  PubMed  Google Scholar 

  32. Cong, F., L. Schweizer, and H. Varmus. (2004) Casein kinase Iepsilon modulates the signaling specificities of dishevelled. Mol Cell Biol. 24, 2000–2011.

    Article  CAS  PubMed  Google Scholar 

  33. Peters, J.M., R.M. McKay, J.P. McKay, and J.M. Graff. (1999) Casein kinase I transduces Wnt signals. Nature. 401, 345–350.

    Article  CAS  PubMed  Google Scholar 

  34. Swiatek, W., I.C. Tsai, L. Klimowski, A. Pepler, J. Barnette, H.J. Yost, et al. (2004) Regulation of casein kinase I epsilon activity by Wnt signaling. J Biol Chem. 279, 13011–13017.

    Article  CAS  PubMed  Google Scholar 

  35. Klein, T.J., A. Jenny, A. Djiane, and M. Mlodzik. (2006) CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. Curr Biol. 16, 1337–1343.

    Article  CAS  PubMed  Google Scholar 

  36. Strutt, H., M.A. Price, and D. Strutt. (2006) Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila. Curr Biol. 16, 1329–1336.

    Article  CAS  PubMed  Google Scholar 

  37. Tao, Q., C. Yokota, H. Puck, M. Kofron, B. Birsoy, D. Yan, et al. (2005) Maternal wnt11 activates the canonical wnt signaling pathway required for axis formation in Xenopus embryos. Cell. 120, 857–871.

    Article  CAS  PubMed  Google Scholar 

  38. Lu, W., V. Yamamoto, B. Ortega, and D. Baltimore. (2004) Mammalian Ryk is a Wnt coreceptor required for stimulation of neu-rite outgrowth. Cell. 119, 97–108.

    Article  CAS  PubMed  Google Scholar 

  39. Hikasa, H., M. Shibata, I. Hiratani, and M. Taira. (2002) The Xenopus receptor tyrosine kinase Xror2 modulates morpho-genetic movements of the axial mesoderm and neuroectoderm via Wnt signaling. Development. 129, 5227–5239.

    CAS  PubMed  Google Scholar 

  40. Mikels, A.J. and R. Nusse. (2006) Purified Wnt5a protein activates or inhibits beta-cat-enin-TCF signaling depending on receptor context. PLoS Biol. 4, e115.

    Article  PubMed  Google Scholar 

  41. Schambony, A. and D. Wedlich. (2007) Wnt-5A/Ror2 regulate expression of XPAPC through an alternative noncanonical signaling pathway. Dev Cell. 12, 779–792.

    Article  CAS  PubMed  Google Scholar 

  42. Keeble, T.R., M.M. Halford, C. Seaman, N. Kee, M. Macheda, R.B. Anderson, et al. (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci. 26, 5840–5848.

    Article  CAS  PubMed  Google Scholar 

  43. Yoshikawa, S., R.D. McKinnon, M. Kokel, and J.B. Thomas. (2003) Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature. 422, 583–588.

    Article  CAS  PubMed  Google Scholar 

  44. Lu, X., A.G. Borchers, C. Jolicoeur, H. Ray-burn, J.C. Baker, and M. Tessier-Lavigne. (2004) PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature. 430, 93–98.

    Article  CAS  PubMed  Google Scholar 

  45. He, X., J.P. Saint-Jeannet, Y. Wang, J. Nathans, I. Dawid, and H. Varmus. (1997) A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science. 275, 1652–1654.

    Article  CAS  PubMed  Google Scholar 

  46. Habas, R., Y. Kato, and X. He. (2001) Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell. 107, 843–854.

    Article  CAS  PubMed  Google Scholar 

  47. Price, M.H., D.M. Roberts, B.M. McCartney, E. Jezuit, and M. Peifer. (2006) Cytoskeletal dynamics and cell signaling during planar polarity establishment in the Drosophila embryonic denticle. J Cell Sci. 119, 403–415.

    Article  CAS  PubMed  Google Scholar 

  48. Harris, K.E. and S.K. Beckendorf. (2007) Different Wnt signals act through the Frizzled and RYK receptors during Drosophila salivary gland migration. Development. 134, 2017–2025.

    Article  CAS  PubMed  Google Scholar 

  49. Wong, L.L. and P.N. Adler. (1993) Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol. 123, 209–221.

    Article  CAS  PubMed  Google Scholar 

  50. Gubb, D. and A. Garcia-Bellido. (1982) A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol. 68, 37–57.

    CAS  PubMed  Google Scholar 

  51. Hall, A. (1998) Rho GTPases and the actin cytoskeleton. Science. 279, 509–514.

    Article  CAS  PubMed  Google Scholar 

  52. Ridley, A.J. and A. Hall. (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 70, 389–399.

    Article  CAS  PubMed  Google Scholar 

  53. Ridley, A.J., H.F. Paterson, C.L. Johnston, D. Diekmann, and A. Hall. (1992) The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 70, 401–410.

    Article  CAS  PubMed  Google Scholar 

  54. Boutros, M., N. Paricio, D.I. Strutt, and M. Mlodzik. (1998) Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Cell. 94, 109–118.

    Article  CAS  PubMed  Google Scholar 

  55. Zhu, S., L. Liu, V. Korzh, Z. Gong, and B.C. Low. (2006) RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cell Signal. 18, 359–372.

    Article  CAS  PubMed  Google Scholar 

  56. Tahinci, E. and K. Symes. (2003) Distinct functions of Rho and Rac are required for convergent extension during Xenopus gas-trulation. Dev Biol. 259, 318–335.

    Article  CAS  PubMed  Google Scholar 

  57. Marlow, F., J. Topczewski, D. Sepich, and L. Solnica-Krezel. (2002) Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and effective convergence and extension movements. Curr Biol. 12, 876–884.

    Article  CAS  PubMed  Google Scholar 

  58. Winter, C.G., B. Wang, A. Ballew, A. Royou, R. Karess, J.D. Axelrod, et al. (2001) Dro-sophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell. 105, 81–91.

    Article  CAS  PubMed  Google Scholar 

  59. Kim, G.H. and J.K. Han. (2005) JNK and ROKalpha function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements. Dev Dyn. 232, 958–968.

    Article  CAS  PubMed  Google Scholar 

  60. Strutt, D.I., U. Weber, and M. Mlodzik. (1997) The role of RhoA in tissue polarity and Frizzled signalling. Nature. 387, 292–295.

    Article  CAS  PubMed  Google Scholar 

  61. Yamanaka, H., T. Moriguchi, N. Masuyama, M. Kusakabe, H. Hanafusa, R. Takada, et al. (2002) JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates. EMBO Rep. 3, 69–75.

    Article  CAS  PubMed  Google Scholar 

  62. Kohn, A.D. and R.T. Moon. (2005) Wnt and calcium signaling: beta-catenin-inde-pendent pathways. Cell Calcium. 38, 439–446.

    Article  CAS  PubMed  Google Scholar 

  63. Slusarski, D.C. and F. Pelegri. (2007) Calcium signaling in vertebrate embryonic patterning and morphogenesis. Dev Biol. 307, 1–13.

    Article  CAS  PubMed  Google Scholar 

  64. Webb, S.E. and A.L. Miller. (2003) Calcium signalling during embryonic development. Nat Rev Mol Cell Biol. 4, 539–551.

    Article  CAS  PubMed  Google Scholar 

  65. Dejmek, J., A. Safholm, C. Kamp Nielsen, T. Andersson, and K. Leandersson. (2006) Wnt-5a/Ca2+-induced NFAT activity is counteracted by Wnt-5a/Yes-Cdc42-casein kinase 1alpha signaling in human mammary epithelial cells. Mol Cell Biol. 26, 6024– 6036.

    Article  CAS  PubMed  Google Scholar 

  66. Ma, L. and H.Y. Wang. (2006) Suppression of cyclic GMP-dependent protein kinase is essential to the Wnt/cGMP/Ca2+ pathway. J Biol Chem. 281, 30990–31001.

    Article  CAS  PubMed  Google Scholar 

  67. Reinhard, E., H. Yokoe, K.R. Niebling, N.L. Allbritton, M.A. Kuhn, and T. Meyer. (1995) Localized calcium signals in early zebrafish development. Dev Biol. 170, 50–61.

    Article  CAS  PubMed  Google Scholar 

  68. Slusarski, D.C., V.G. Corces, and R.T. Moon. (1997) Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phos-phatidylinositol signalling. Nature. 390, 410–413.

    Article  CAS  PubMed  Google Scholar 

  69. Slusarski, D.C., J. Yang-Snyder, W.B. Busa, and R.T. Moon. (1997) Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev Biol. 182, 114–120.

    Article  CAS  PubMed  Google Scholar 

  70. Gilland, E., A.L. Miller, E. Karplus, R. Baker, and S.E. Webb. (1999) Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation. Proc Natl Acad Sci U S A. 96, 157–161.

    Article  CAS  PubMed  Google Scholar 

  71. Wallingford, J.B., A.J. Ewald, R.M. Harland, and S.E. Fraser. (2001) Calcium signaling during convergent extension in Xenopus. Curr Biol. 11, 652–661.

    Article  CAS  PubMed  Google Scholar 

  72. Westfall, T.A., R. Brimeyer, J. Twedt, J. Gladon, A. Olberding, M. Furutani-Seiki, et al. (2003) Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity. J Cell Biol. 162, 889–898.

    Article  CAS  PubMed  Google Scholar 

  73. Kuhl, M., L.C. Sheldahl, C.C. Malbon, and R.T. Moon. (2000) Ca(2+)/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.

    Article  CAS  PubMed  Google Scholar 

  74. Sheldahl, L.C., D.C. Slusarski, P. Pandur, J.R. Miller, M. Kuhl, and R.T. Moon. (2003) Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos. J Cell Biol. 161, 769–777.

    Article  CAS  PubMed  Google Scholar 

  75. Sheldahl, L.C., M. Park, C.C. Malbon, and R.T. Moon. (1999) Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 9, 695–698.

    Article  CAS  PubMed  Google Scholar 

  76. Saneyoshi, T., S. Kume, Y. Amasaki, and K. Mikoshiba. (2002) The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature. 417, 295–299.

    Article  CAS  PubMed  Google Scholar 

  77. Westfall, T.A., B. Hjertos, and D.C. Slusarski. (2003) Requirement for intracellular calcium modulation in zebrafish dorsal-ventral patterning. Dev Biol. 259, 380–391.

    Article  CAS  PubMed  Google Scholar 

  78. Gwak, J., M. Cho, S.J. Gong, J. Won, D.E. Kim, E.Y. Kim, et al. (2006) Protein-kinase-C-mediated beta-catenin phosphorylation negatively regulates the Wnt/beta-catenin pathway. J Cell Sci. 119, 4702–4709.

    Article  CAS  PubMed  Google Scholar 

  79. Ishitani, T., S. Kishida, J. Hyodo-Miura, N. Ueno, J. Yasuda, M. Waterman, et al. (2003) The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. Mol Cell Biol. 23, 131–139.

    Article  CAS  PubMed  Google Scholar 

  80. Ishitani, T., J. Ninomiya-Tsuji, and K. Matsumoto. (2003) Regulation of lym-phoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphoryla-tion in Wnt/beta-catenin signaling. Mol Cell Biol. 23, 1379–1389.

    Article  CAS  PubMed  Google Scholar 

  81. Ishitani, T., J. Ninomiya-Tsuji, S. Nagai, M. Nishita, M. Meneghini, N. Barker, et al. (1999) The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Nature. 399, 798–802.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Howard Hughes Medical Institute and the National Institutes of Health (NIH) RO1 GM073887-03 to RTM.

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, Department of Pharmacology, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA

    Richard G. James, William H. Conrad & Randall T. Moon

Authors
  1. Richard G. James
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William H. Conrad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Randall T. Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Melbourne, Parkville, Victoria, VIC 3010, Australia

    Elizabeth Vincan PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

James, R.G., Conrad, W.H., Moon, R.T. (2008). β-Catenin-Independent Wnt Pathways: Signals, Core Proteins, and Effectors. In: Vincan, E. (eds) Wnt Signaling. Methods in Molecular Biology™, vol 468. Humana Press. https://doi.org/10.1007/978-1-59745-249-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-249-6_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-912-3

  • Online ISBN: 978-1-59745-249-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation