Animal cells and systems

  • 제13권1호
  • /
  • Pages.9-15
  • /
  • 2009
  • /
  • 1976-8354(pISSN)
  • /
  • 2151-2485(eISSN)
한국통합생물학회 (The Korean Society for Integrative Biology)
권호 표지

Identification of WDR7 as a Novel Downstream Target of the EphA8-Odin Signaling Complex

  • Park, Eun-Jeong (Department of Biological Science, Sookmyung Women's University) ;
  • Park, Soo-Chul (Department of Biological Science, Sookmyung Women's University)
  • 발행 : 2009.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Eph receptors and their ephrin ligands have been implicated in a variety of cellular processes such as cellular morphogenesis and motility. Our previous studies demonstrated that Odin, one of the Anks family proteins, functions as a scaffolding protein of the EphA8 signaling pathway leading to modulation of cell migration or axonal outgrowth. Here we show that WDR7 is associated with Odin and that it is possibly implicated in the EphA8 signaling pathway. WD40 repeats present in the COOH-terminal region of WDR7 appear to be crucial for its association with Odin, whereas the binding motif of Odin is located in between ankyrin repeats and PTB domain. Co-immunoprecipitation experiments revealed that association of WDR7 with Odin is enhanced by ephrin ligand treatment, possibly through forming large protein complexes including both EphA8 and ephrin-A5. Consistently, immunofluorescence staining experiments suggested that WDR7 constitute a component of the large protein complexes containing Odin, EphA8 and ephrin-A5. Taken together, our results suggest the WDR7-Odin complexes might be involved in the signaling pathway downstream of the EphA8 receptor.

키워드

참고문헌

  1. Choi SA and Park SC (1999) Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. Oncogene 18: 5413-5422 https://doi.org/10.1038/sj.onc.1202917
  2. de Hostos EL, Bradtke B, Lottspeich F, Guggenheim R, and Gerisch G (1991) Coronin, an actin binding protein of Dictyostelium discoideum localized to cell surface projections, has sequence similarities to G protein beta subunits. EMBO J 10: 4097-4104
  3. Egea J and Klein R (2007) Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol 17: 230-238 https://doi.org/10.1016/j.tcb.2007.03.004
  4. Feldman RM, Correll CC, Kaplan KB, and Deshaies RJ (1997) A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell 91: 211-230 https://doi.org/10.1016/S0092-8674(00)80404-3
  5. Ghersi E, Noviello C, and D'Adamio L (2004) Amyloid-$\beta$ protein precursor (A$\beta$PP) intracellular domain-associated protein-1 proteins bind to A$\beta$PP and modulate its processing in an isoform-specific manner. J Biol Chem 279: 49105-40112 https://doi.org/10.1074/jbc.M405329200
  6. Gu CG and Park SC (2001) The EphA8 receptor regulates integrin activity through p110$\gamma$ phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol Cell Biol 21: 4579-4597 https://doi.org/10.1128/MCB.21.14.4579-4597.2001
  7. Himanen J-P, Saha N, and Nikolov DB (2007) Cell-cell signaling via Eph receptors and ephrins. Curr Opin Cell Biol 19: 534-542 https://doi.org/10.1016/j.ceb.2007.08.004
  8. Hoey T, Weinzierl RO, Gill G, Chen JL, Dynlacht BD, and Tjian R (1993) Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Cell 72: 247-260 https://doi.org/10.1016/0092-8674(93)90664-C
  9. Kawabe H, Sakisaka T, Yasumi M, Shingai T, Izumi G, Nagano F, Deguchi-Tawarada M, Takeuchi M, Nakanishi H, and Takai Y (2003) A novel rabconnectin-3-binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca$^{2+}$-dependent exocytosis of neurotransmitter. Genes Cells 8: 537-546 https://doi.org/10.1046/j.1365-2443.2003.00655.x
  10. Kullander K and Klein R (2002) Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3: 475-486 https://doi.org/10.1038/nrm856
  11. Li D and Roberts R (2001) WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci 58: 2085-2097 https://doi.org/10.1007/PL00000838
  12. Nagano F, Kawabe H, Nakanishi H, Shinohara M, Deguchi-Tawarada M, Takeuchi M, Sasaki T, and Takai Y (2002) Rabconnectin-3, a novel protein that binds both GDP/GTP exchange protein and GTPase-activating protein for Rab3 small G protein family. J Biol Chem 277: 9629-9632 https://doi.org/10.1074/jbc.C100730200
  13. Palmer A and Klein R (2003) Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function. Genes Dev 17: 1429-1450 https://doi.org/10.1101/gad.1093703
  14. Pandey A, Blagoev B, Kratchmarova I, Fernandez M, Nielsen M, Kristiansen TZ, Ohara O, Podtelejnikov AV, Roche S, Lodish HF, and Mann M (2002) Cloning of a novel phosphotyrosine binding domain containing molecule, Odin, involved in signaling by receptor tyrosine kinases. Oncogene 21: 8029-8036 https://doi.org/10.1038/sj.onc.1205988
  15. Pasquale EB (2005) Eph receptor signalling casts a wide net on cell behaviour. Nat Rev Mol Cell Biol 6: 462-475 https://doi.org/10.1038/nrm1662
  16. Pasquale EB (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell 133: 38-52 https://doi.org/10.1016/j.cell.2008.03.011
  17. Pryer NK, Salama NR, Schekman R, and Kaiser CA (1993) Cytosolic Sec13p complex is required for vesicle formation from the endoplasmic reticulum in vitro. J Cell Biol 120: 865-875 https://doi.org/10.1083/jcb.120.4.865
  18. Sanders S, Keck-Waggoner CL, Zimonjic DB, Popescu NC, and Thorgeirsson SS (2000) Assignment of WDR7 (alias TRAG, TGF-beta resistance associated gene) to orthologous regions of human chromosome 18q21.1$\rightarrow$q22 and mouse chromosome 18D.1-E.3 by fluorescence in situ hybridization. Cytogenet Cell Genet 88: 324-325 https://doi.org/10.1159/000015520
  19. Shin JD, Gu CG, Park EJ, and Park SC (2007) Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function. Mol Cell Biol 27: 8113-8126 https://doi.org/10.1128/MCB.00794-07
  20. Smith TF, Gaitatzes C, Saxena K, and Neer EJ (1999) The WD repeat: a common architecture for diverse functions. Trends Biochem Sci 24: 181-185 https://doi.org/10.1016/S0968-0004(99)01384-5
  21. Vaisman N, Tsouladze A, Robzyk K, Ben-Yehuda S, Kupiec M, and Kassir Y (1995) The role of Saccharomyces cerevisiae Cdc40p in DNA replication and mitotic spindle formation and/or maintenance. Mol Gen Genet 247: 123-136 https://doi.org/10.1007/BF00705642
  22. van der Voorn L, and Ploegh HL (1992) The WD-40 repeat. FEBS Lett 307: 131-134 https://doi.org/10.1016/0014-5793(92)80751-2
  23. Williams FE, Varanasi U, and Trumbly RJ (1991) The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex. Mol Cell Biol 11: 3307-3316 https://doi.org/10.1128/MCB.11.6.3307