DOI QR코드

DOI QR Code

EphrinB1 interacts with the transcriptional co-repressor Groucho/xTLE4

  • Kamata, Teddy (Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick) ;
  • Bong, Yong-Sik (Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick) ;
  • Mood, Kathleen (Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick) ;
  • Park, Mae-Ja (Department of Anatomy, School of Medicine, Kyungpook National University) ;
  • Nishanian, Tagvor G. (Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick) ;
  • Lee, Hyun-Shik (Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick)
  • Received : 2010.11.29
  • Accepted : 2010.12.23
  • Published : 2011.03.31

Abstract

Ephrin signaling is involved in various morphogenetic events, such as axon guidance, hindbrain segmentation, and angiogenesis. We conducted a yeast two-hybrid screen using the intracellular domain (ICD) of EphrinB1 to gain biochemical insight into the function of the EphrinB1 ICD. We identified the transcriptional co-repressor xTLE1/Groucho as an EphrinB1 interacting protein. Whole-mount in situ hybridization of Xenopus embryos confirmed the co-localization of EphrinB1 and a Xenopus counterpart to TLE1, xTLE4, during various stages of development. The EphrinB1/xTLE4 interaction was confirmed by co-immunoprecipitation experiments. Further characterization of the interaction revealed that the carboxy-terminal PDZ binding motif of EphrinB1 and the SP domain of xTLE4 are required for binding. Additionally, phosphorylation of EphrinB1 by a constitutively activated fibroblast growth factor receptor resulted in loss of the interaction, suggesting that the interaction is modulated by tyrosine phosphorylation of the EphrinB1 ICD.

Keywords

References

  1. Palmer, A. and Klein, R. (2003) Multiple roles of ephrinsin morphogenesis, neuronal networking, and brainfunction. Genes Dev. 17, 1429-1450. https://doi.org/10.1101/gad.1093703
  2. Clevers, H. and Batlle, E. (2006) EphB/EphrinB receptorsand Wnt signaling in colorectal cancer. Cancer Res. 66,2-5. https://doi.org/10.1158/0008-5472.CAN-05-3849
  3. Heroult, M., Schaffner, F. and Augustin, H. G. (2006) Ephreceptor and ephrin ligand-mediated interactions duringangiogenesis and tumor progression. Exp. Cell Res. 312,642-650. https://doi.org/10.1016/j.yexcr.2005.10.028
  4. Holland, S. J., Gale, N. W., Mbamalu, G., Yancopoulos,G. D., Henkemeyer, M. and Pawson, T. (1996) Bidirectionalsignalling through the EPH-family receptor Nuk and itstransmembrane ligands. Nature 383, 722-725. https://doi.org/10.1038/383722a0
  5. Bruckner, K., Pasquale, E. B. and Klein, R. (1997) Tyrosinephosphorylation of transmembrane ligands for Eph receptors.Science 275, 1640-1643. https://doi.org/10.1126/science.275.5306.1640
  6. Chong, L. D., Park, E. K., Latimer, E., Friesel, R. and Daar,I. O. (2000) Fibroblast growth factor receptor-mediatedrescue of x-ephrin B1-induced cell dissociation inXenopus embryos. Mol. Cell Biol. 20, 724-734. https://doi.org/10.1128/MCB.20.2.724-734.2000
  7. Tanaka, M., Kamata, R. and Sakai, R. (2005) Phosphorylationof ephrin-B1 via the interaction with claudin followingcell-cell contact formation. EMBO J. 24, 3700-3711. https://doi.org/10.1038/sj.emboj.7600831
  8. Cowan, C. A. and Henkemeyer, M. (2001) The SH2/SH3adaptor Grb4 transduces B-ephrin reverse signals. Nature413, 174-179. https://doi.org/10.1038/35093123
  9. Bong, Y. S., Lee, H. S., Carim-Todd, L., Mood, K.,Nishanian, T. G., Tessarollo, L. and Daar, I. O. (2007)ephrinB1 signals from the cell surface to the nucleus byrecruitment of STAT3. Proc. Natl. Acad. Sci. U.S.A. 104,17305-17310. https://doi.org/10.1073/pnas.0702337104
  10. Lu, Q., Sun, E. E., Klein, R. S. and Flanagan, J. G. (2001)Ephrin-B reverse signaling is mediated by a novelPDZ-RGS protein and selectively inhibits G protein- coupledchemoattraction. Cell 105, 69-79. https://doi.org/10.1016/S0092-8674(01)00297-5
  11. Sarkar, D., Boukerche, H., Su, Z. Z. and Fisher, P. B.(2004) mda-9/syntenin: recent insights into a novel cellsignaling and metastasis-associated gene. Pharmacol.Ther. 104, 101-115. https://doi.org/10.1016/j.pharmthera.2004.08.004
  12. Lin, D., Gish, G. D., Songyang, Z. and Pawson, T. (1999)The carboxyl terminus of B class ephrins constitutes aPDZ domain binding motif. J. Biol. Chem. 274, 3726-3733. https://doi.org/10.1074/jbc.274.6.3726
  13. Lee, H. S., Bong, Y. S., Moore, K. B., Soria, K., Moody, S.A. and Daar, I. O. (2006) Dishevelled mediates ephrinB1signalling in the eye field through the planar cell polaritypathway. Nat. Cell Biol. 8, 55-63. https://doi.org/10.1038/ncb1344
  14. Lee, H. S., Mood, K., Battu, G., Ji, Y. J., Singh, A. andDaar, I. O. (2009) Fibroblast growth factor receptor-inducedphosphorylation of ephrinB1 modulates its interactionwith Dishevelled. Mol. Biol. Cell 20, 124-133. https://doi.org/10.1091/mbc.E08-06-0662
  15. Lee, H. S., Nishanian, T. G., Mood, K., Bong, Y. S. andDaar, I. O. (2008) EphrinB1 controls cell-cell junctionsthrough the Par polarity complex. Nat. Cell Biol. 10, 979-986. https://doi.org/10.1038/ncb1758
  16. Hasson, P. and Paroush, Z. (2006) Crosstalk between theEGFR and other signalling pathways at the level of theglobal transcriptional corepressor Groucho/TLE. Br. J.Cancer 94, 771-775. https://doi.org/10.1038/sj.bjc.6603019
  17. Molenaar, M., Brian, E., Roose, J., Clevers, H. and Destree, O. (2000) Differential expression of the Groucho-relatedgenes 4 and 5 during early development ofXenopus laevis. Mech. Dev. 91, 311-315. https://doi.org/10.1016/S0925-4773(99)00259-2
  18. Jones, T. L., Karavanova, I., Chong, L., Zhou, R. P. andDaar, I. O. (1997) Identification of XLerk, an Eph family ligandregulated during mesoderm induction and neurogenesisin Xenopus laevis. Oncogene. 14, 2159-2166. https://doi.org/10.1038/sj.onc.1201082
  19. Gasperowicz, M. and Otto, F. (2005) Mammalian Grouchohomologs: redundancy or specificity? J. Cell Biochem. 95,670-687. https://doi.org/10.1002/jcb.20476
  20. Brantjes, H., Roose, J., van De Wetering, M. and Clevers,H. (2001) All Tcf HMG box transcription factors interactwith Groucho-related co-repressors. Nucleic. Acids. Res.29, 1410-1419. https://doi.org/10.1093/nar/29.7.1410
  21. Nuthall, H. N., Joachim, K., Palaparti, A. and Stifani, S.(2002) A role for cell cycle-regulated phosphorylation inGroucho-mediated transcriptional repression. J. Biol. Chem.277, 51049-51057. https://doi.org/10.1074/jbc.M111660200
  22. Nuthall, H. N., Joachim, K. and Stifani, S. (2004) Phosphorylationof serine 239 of Groucho/TLE1 by proteinkinase CK2 is important for inhibition of neuronal differentiation.Mol. Cell Biol. 24, 8395-8407. https://doi.org/10.1128/MCB.24.19.8395-8407.2004
  23. Choi, C. Y., Kim, Y. H., Kim, Y. O., Park, S. J., Kim, E. A.,Riemenschneider, W., Gajewski, K., Schulz, R. A. andKim, Y. (2005) Phosphorylation by the DHIPK2 proteinkinase modulates the corepressor activity of Groucho. J.Biol. Chem. 280, 21427-21436. https://doi.org/10.1074/jbc.M500496200
  24. Yamagata, T., Maki, K. and Mitani, K. (2005) Runx1/AML1in normal and abnormal hematopoiesis. Int. J. Hematol.82, 1-8. https://doi.org/10.1532/IJH97.05075
  25. Huang, W., Yang, S., Shao, J. and Li, Y. P. (2007)Signaling and transcriptional regulation in osteoblast commitmentand differentiation. Front Biosci. 12, 3068-3092. https://doi.org/10.2741/2296
  26. Levanon, D., Bettoun, D., Harris-Cerruti, C., Woolf, E.,Negreanu, V., Eilam, R., Bernstein, Y., Goldenberg, D.,Xiao, C., Fliegauf, M., Kremer, E., Otto, F., Brenner, O.,Lev-Tov, A. and Groner, Y. (2002) The Runx3 transcriptionfactor regulates development and survival of TrkCdorsal root ganglia neurons. EMBO J. 21, 3454-3463. https://doi.org/10.1093/emboj/cdf370
  27. Pickles, L. M., Roe, S. M., Hemingway, E. J., Stifani, S.and Pearl, L. H. (2002) Crystal structure of the C-terminalWD40 repeat domain of the human Groucho/TLE1 transcriptionalcorepressor. Structure 10, 751-761. https://doi.org/10.1016/S0969-2126(02)00768-2
  28. Stifani, S., Blaumueller, C. M., Redhead, N. J., Hill, R. E.and Artavanis-Tsakonas, S. (1992) Human homologs of aDrosophila Enhancer of split gene product define a novelfamily of nuclear proteins. Nat. Genet. 2, 119-127. https://doi.org/10.1038/ng1092-119
  29. Javed, A., Guo, B., Hiebert, S., Choi, J. Y., Green, J.,Zhao, S. C., Osborne, M. A., Stifani, S., Stein, J. L., Lian, J.B., van Wijnen, A. J. and Stein, G. S. (2000) Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/ PEBP2(alpha)) dependent activation of tissue-specific gene transcription. J. Cell Sci.113( Pt 12), 2221-2231.
  30. Liu, F., Liu, Y., Li, D., Zhu, Y., Ouyang, W., Xie, X. andJin, B. (2002) The transcription co-repressor TLE1 interactedwith the intracellular region of gpl30 through its Qdomain. Mol. Cell Biochem. 232, 163-167. https://doi.org/10.1023/A:1014880813692
  31. Georgakopoulos, A., Litterst, C., Ghersi, E., Baki, L., Xu,C., Serban, G. and Robakis, N. K. (2006) Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-inducedSrc phosphorylation and signaling. EMBO J. 25, 1242-1252. https://doi.org/10.1038/sj.emboj.7601031
  32. Tomita, T., Tanaka, S., Morohashi, Y. and Iwatsubo, T.(2006) Presenilin-dependent intramembrane cleavage ofephrin-B1. Mol. Neurodegener. 1, 2. https://doi.org/10.1186/1750-1326-1-2

Cited by

  1. Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of tgfß3 vol.230, pp.12, 2015, https://doi.org/10.1002/jcp.25025