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. 1999 Apr 15;18(8):2208–2217. doi: 10.1093/emboj/18.8.2208

The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila.

A Gallet 1, C Angelats 1, A Erkner 1, B Charroux 1, L Fasano 1, S Kerridge 1
PMCID: PMC1171304  PMID: 10205174

Abstract

Wnt signalling is a key pathway for tissue patterning during animal development. In Drosophila, the Wnt protein Wingless acts to stabilize Armadillo inside cells where it binds to at least two DNA-binding factors which regulate specific target genes. One Armadillo-binding protein in Drosophila is the zinc finger protein Teashirt. Here we show that Wingless signalling promotes the phosphorylation and the nuclear accumulation of Teashirt. This process requires the binding of Teashirt to the C-terminal end of Armadillo. Finally, we present evidence that the serine/threonine kinase Shaggy is associated with Teashirt in a complex. We discuss these results with respect to current models of Armadillo/beta-catenin action for the transmission of the Wingless/Wnt pathway.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aberle H., Bauer A., Stappert J., Kispert A., Kemler R. beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 1997 Jul 1;16(13):3797–3804. doi: 10.1093/emboj/16.13.3797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexandre E., Graba Y., Fasano L., Gallet A., Perrin L., De Zulueta P., Pradel J., Kerridge S., Jacq B. The Drosophila teashirt homeotic protein is a DNA-binding protein and modulo, a HOM-C regulated modifier of variegation, is a likely candidate for being a direct target gene. Mech Dev. 1996 Oct;59(2):191–204. doi: 10.1016/0925-4773(96)00594-1. [DOI] [PubMed] [Google Scholar]
  3. Bejsovec A., Martinez Arias A. Roles of wingless in patterning the larval epidermis of Drosophila. Development. 1991 Oct;113(2):471–485. doi: 10.1242/dev.113.2.471. [DOI] [PubMed] [Google Scholar]
  4. Bhanot P., Brink M., Samos C. H., Hsieh J. C., Wang Y., Macke J. P., Andrew D., Nathans J., Nusse R. A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature. 1996 Jul 18;382(6588):225–230. doi: 10.1038/382225a0. [DOI] [PubMed] [Google Scholar]
  5. Bhat K. M. frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis. Cell. 1998 Dec 23;95(7):1027–1036. doi: 10.1016/s0092-8674(00)81726-2. [DOI] [PubMed] [Google Scholar]
  6. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  7. Brunner E., Peter O., Schweizer L., Basler K. pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature. 1997 Feb 27;385(6619):829–833. doi: 10.1038/385829a0. [DOI] [PubMed] [Google Scholar]
  8. Cadigan K. M., Fish M. P., Rulifson E. J., Nusse R. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell. 1998 May 29;93(5):767–777. doi: 10.1016/s0092-8674(00)81438-5. [DOI] [PubMed] [Google Scholar]
  9. Cadigan K. M., Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997 Dec 15;11(24):3286–3305. doi: 10.1101/gad.11.24.3286. [DOI] [PubMed] [Google Scholar]
  10. Cavallo R. A., Cox R. T., Moline M. M., Roose J., Polevoy G. A., Clevers H., Peifer M., Bejsovec A. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature. 1998 Oct 8;395(6702):604–608. doi: 10.1038/26982. [DOI] [PubMed] [Google Scholar]
  11. Clevers H., van de Wetering M. TCF/LEF factor earn their wings. Trends Genet. 1997 Dec;13(12):485–489. doi: 10.1016/s0168-9525(97)01305-x. [DOI] [PubMed] [Google Scholar]
  12. Cox R. T., Kirkpatrick C., Peifer M. Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. J Cell Biol. 1996 Jul;134(1):133–148. doi: 10.1083/jcb.134.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cox R. T., Peifer M. Wingless signaling: the inconvenient complexities of life. Curr Biol. 1998 Feb 12;8(4):R140–R144. doi: 10.1016/s0960-9822(98)70081-8. [DOI] [PubMed] [Google Scholar]
  14. Dougan S., DiNardo S. Drosophila wingless generates cell type diversity among engrailed expressing cells. Nature. 1992 Nov 26;360(6402):347–350. doi: 10.1038/360347a0. [DOI] [PubMed] [Google Scholar]
  15. Fagotto F., Glück U., Gumbiner B. M. Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin. Curr Biol. 1998 Feb 12;8(4):181–190. doi: 10.1016/s0960-9822(98)70082-x. [DOI] [PubMed] [Google Scholar]
  16. Fasano L., Röder L., Coré N., Alexandre E., Vola C., Jacq B., Kerridge S. The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs. Cell. 1991 Jan 11;64(1):63–79. doi: 10.1016/0092-8674(91)90209-h. [DOI] [PubMed] [Google Scholar]
  17. Gallet A., Erkner A., Charroux B., Fasano L., Kerridge S. Trunk-specific modulation of wingless signalling in Drosophila by teashirt binding to armadillo. 1998 Jul 30-Aug 13Curr Biol. 8(16):893–902. doi: 10.1016/s0960-9822(07)00369-7. [DOI] [PubMed] [Google Scholar]
  18. Hays R., Gibori G. B., Bejsovec A. Wingless signaling generates pattern through two distinct mechanisms. Development. 1997 Oct;124(19):3727–3736. doi: 10.1242/dev.124.19.3727. [DOI] [PubMed] [Google Scholar]
  19. Hooper J. E. Distinct pathways for autocrine and paracrine Wingless signalling in Drosophila embryos. Nature. 1994 Dec 1;372(6505):461–464. doi: 10.1038/372461a0. [DOI] [PubMed] [Google Scholar]
  20. Hülsken J., Birchmeier W., Behrens J. E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J Cell Biol. 1994 Dec;127(6 Pt 2):2061–2069. doi: 10.1083/jcb.127.6.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Klingensmith J., Noll E., Perrimon N. The segment polarity phenotype of Drosophila involves differential tendencies toward transformation and cell death. Dev Biol. 1989 Jul;134(1):130–145. doi: 10.1016/0012-1606(89)90084-5. [DOI] [PubMed] [Google Scholar]
  22. Korinek V., Barker N., Morin P. J., van Wichen D., de Weger R., Kinzler K. W., Vogelstein B., Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997 Mar 21;275(5307):1784–1787. doi: 10.1126/science.275.5307.1784. [DOI] [PubMed] [Google Scholar]
  23. Loureiro J., Peifer M. Roles of Armadillo, a Drosophila catenin, during central nervous system development. Curr Biol. 1998 May 21;8(11):622–632. doi: 10.1016/s0960-9822(98)70249-0. [DOI] [PubMed] [Google Scholar]
  24. Manoukian A. S., Yoffe K. B., Wilder E. L., Perrimon N. The porcupine gene is required for wingless autoregulation in Drosophila. Development. 1995 Dec;121(12):4037–4044. doi: 10.1242/dev.121.12.4037. [DOI] [PubMed] [Google Scholar]
  25. Martizez Arias A., Baker N. E., Ingham P. W. Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. Development. 1988 May;103(1):157–170. doi: 10.1242/dev.103.1.157. [DOI] [PubMed] [Google Scholar]
  26. Miller J. R., Moon R. T. Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 1996 Oct 15;10(20):2527–2539. doi: 10.1101/gad.10.20.2527. [DOI] [PubMed] [Google Scholar]
  27. Molenaar M., van de Wetering M., Oosterwegel M., Peterson-Maduro J., Godsave S., Korinek V., Roose J., Destrée O., Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391–399. doi: 10.1016/s0092-8674(00)80112-9. [DOI] [PubMed] [Google Scholar]
  28. Müller H. A., Samanta R., Wieschaus E. Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development. 1999 Feb;126(3):577–586. doi: 10.1242/dev.126.3.577. [DOI] [PubMed] [Google Scholar]
  29. Neumann C., Cohen S. Morphogens and pattern formation. Bioessays. 1997 Aug;19(8):721–729. doi: 10.1002/bies.950190813. [DOI] [PubMed] [Google Scholar]
  30. Noordermeer J., Johnston P., Rijsewijk F., Nusse R., Lawrence P. A. The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. Development. 1992 Nov;116(3):711–719. doi: 10.1242/dev.116.3.711. [DOI] [PubMed] [Google Scholar]
  31. Nüsslein-Volhard C., Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980 Oct 30;287(5785):795–801. doi: 10.1038/287795a0. [DOI] [PubMed] [Google Scholar]
  32. Orsulic S., Peifer M. 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. 1996 Sep;134(5):1283–1300. doi: 10.1083/jcb.134.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pai L. M., Kirkpatrick C., Blanton J., Oda H., Takeichi M., Peifer M. Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo. J Biol Chem. 1996 Dec 13;271(50):32411–32420. doi: 10.1074/jbc.271.50.32411. [DOI] [PubMed] [Google Scholar]
  34. Pai L. M., Orsulic S., Bejsovec A., Peifer M. Negative regulation of Armadillo, a Wingless effector in Drosophila. Development. 1997 Jun;124(11):2255–2266. doi: 10.1242/dev.124.11.2255. [DOI] [PubMed] [Google Scholar]
  35. Peifer M., Berg S., Reynolds A. B. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994 Mar 11;76(5):789–791. doi: 10.1016/0092-8674(94)90353-0. [DOI] [PubMed] [Google Scholar]
  36. Peifer M., Orsulic S., Sweeton D., Wieschaus E. A role for the Drosophila segment polarity gene armadillo in cell adhesion and cytoskeletal integrity during oogenesis. Development. 1993 Aug;118(4):1191–1207. doi: 10.1242/dev.118.4.1191. [DOI] [PubMed] [Google Scholar]
  37. Peifer M., Pai L. M., Casey M. Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. Dev Biol. 1994 Dec;166(2):543–556. doi: 10.1006/dbio.1994.1336. [DOI] [PubMed] [Google Scholar]
  38. Peifer M., Sweeton D., Casey M., Wieschaus E. wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development. 1994 Feb;120(2):369–380. doi: 10.1242/dev.120.2.369. [DOI] [PubMed] [Google Scholar]
  39. Peifer M., Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990 Dec 21;63(6):1167–1176. doi: 10.1016/0092-8674(90)90413-9. [DOI] [PubMed] [Google Scholar]
  40. Perrimon N. The genetic basis of patterned baldness in Drosophila. Cell. 1994 Mar 11;76(5):781–784. doi: 10.1016/0092-8674(94)90351-4. [DOI] [PubMed] [Google Scholar]
  41. Riggleman B., Schedl P., Wieschaus E. Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell. 1990 Nov 2;63(3):549–560. doi: 10.1016/0092-8674(90)90451-j. [DOI] [PubMed] [Google Scholar]
  42. Roose J., Molenaar M., Peterson J., Hurenkamp J., Brantjes H., Moerer P., van de Wetering M., Destrée O., Clevers H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature. 1998 Oct 8;395(6702):608–612. doi: 10.1038/26989. [DOI] [PubMed] [Google Scholar]
  43. Rubinfeld B., Albert I., Porfiri E., Fiol C., Munemitsu S., Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996 May 17;272(5264):1023–1026. doi: 10.1126/science.272.5264.1023. [DOI] [PubMed] [Google Scholar]
  44. Ruel L., Bourouis M., Heitzler P., Pantesco V., Simpson P. Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. Nature. 1993 Apr 8;362(6420):557–560. doi: 10.1038/362557a0. [DOI] [PubMed] [Google Scholar]
  45. Röder L., Vola C., Kerridge S. The role of the teashirt gene in trunk segmental identity in Drosophila. Development. 1992 Aug;115(4):1017–1033. doi: 10.1242/dev.115.4.1017. [DOI] [PubMed] [Google Scholar]
  46. Siegfried E., Chou T. B., Perrimon N. wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Cell. 1992 Dec 24;71(7):1167–1179. doi: 10.1016/s0092-8674(05)80065-0. [DOI] [PubMed] [Google Scholar]
  47. Waltzer L., Bienz M. Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling. Nature. 1998 Oct 1;395(6701):521–525. doi: 10.1038/26785. [DOI] [PubMed] [Google Scholar]
  48. Yano R., Oakes M. L., Tabb M. M., Nomura M. Yeast Srp1p has homology to armadillo/plakoglobin/beta-catenin and participates in apparently multiple nuclear functions including the maintenance of the nucleolar structure. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6880–6884. doi: 10.1073/pnas.91.15.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zhang J., Carthew R. W. Interactions between Wingless and DFz2 during Drosophila wing development. Development. 1998 Aug;125(16):3075–3085. doi: 10.1242/dev.125.16.3075. [DOI] [PubMed] [Google Scholar]
  50. de Zulueta P., Alexandre E., Jacq B., Kerridge S. Homeotic complex and teashirt genes co-operate to establish trunk segmental identities in Drosophila. Development. 1994 Aug;120(8):2287–2296. doi: 10.1242/dev.120.8.2287. [DOI] [PubMed] [Google Scholar]
  51. van de Wetering M., Cavallo R., Dooijes D., van Beest M., van Es J., Loureiro J., Ypma A., Hursh D., Jones T., Bejsovec A. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 1997 Mar 21;88(6):789–799. doi: 10.1016/s0092-8674(00)81925-x. [DOI] [PubMed] [Google Scholar]

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