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Eph receptors and ephrin ligands: embryogenesis to tumorigenesis

Oncogene volume 19, pages 5614–5619 (2000)Cite this article

Abstract

Protein tyrosine kinase genes are the largest family of oncogenes. This is not surprising since tyrosine kinases are important components of signal transduction pathways that control cell shape, proliferation, differentiation, and migration. At 14 distinct members, the Eph kinases constitute the largest family of receptor tyrosine kinases. Although they have been most intensively studied for their roles in embryonic development, increasing evidence also implicates Eph family proteins in cancer. This review will address the recent progress in understanding the function of Eph receptors in normal development and how disregulation of these functions could promote tumorigenesis.

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References

  • Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W and Klein R. . 1999 Genes Dev. 13: 295–306.

  • Andres AC, Reid HH, Zurcher G, Blaschke RJ, Albrecht D and Ziemiecki A. . 1994 Oncogene 9: 1461–1467.

  • Banyard J, Anand-Apte B, Symons M and Zetter BR. . 2000 Oncogene 19: 580–591.

  • Bennett BD, Wang Z, Kuang WJ, Wang A, Groopman JE, Goeddel DV and Scadden DT. . 1994 J. Biol. Chem. 269: 14211–14218.

  • Berclaz G, Andres AC, Albrecht D, Dreher E, Ziemiecki A, Gusterson BA and Crompton MR. . 1996 Biochem. Biophys. Res. Commun. 226: 869–875.

  • Birgbauer E, Cowan CA, Sretavan DW and Henkemeyer M. . 2000 Development 127: 1231–1241.

  • Bohme B, Holtrich U, Wolf G, Luzius H, Grzeschik KH, Strebhardt K and Rubsamen-Waigmann H. . 1993 Oncogene 8: 2857–2862.

  • Bruckner K and Klein R. . 1998 Curr. Opin. Neurobiol. 8: 375–382.

  • Bruckner K, Pasquale EB and Klein R. . 1997 Science 275: 1640–1643.

  • Buchert M, Schneider S, Meskenaite V, Adams MT, Canaani E, Baechi T, Moelling K and Hovens CM. . 1999 J. Cell. Biol. 144: 361–371.

  • Cheng HJ and Flanagan JG. . 1994 Cell 79: 157–168.

  • Cowan CA, Yokoyama N, Bianchi LM, Henkemeyer M and Fritzsch B. . 2000 Neuron 26: 417–430.

  • Craven SE and Bredt DS. . 1998 Cell 93: 495–498.

  • Daniel TO, Stein E, Cerretti DP, St John PL, Robert B and Abrahamson DR. . 1996 Kidney Int. Suppl. 57: S73–S81.

  • Davy A, Gale NW, Murray EW, Klinghoffer RA, Soriano P, Feuerstein C and Robbins SM. . 1999 Genes Dev. 13: 3125–3135.

  • Dodelet VC, Pazzagli C, Zisch AH, Hauser CA and Pasquale EB. . 1999 J. Biol. Chem. 274: 31941–31946.

  • Donoghue MJ and Rakic P. . 1999 J. Neurosci. 19: 5967–5979.

  • Dottori M, Hartley L, Galea M, Paxinos G, Polizzotto M, Kilpatrick T, Bartlett PF, Murphy M, Kontgen F and Boyd AW. . 1998 Proc. Natl. Acad. Sci. USA 95: 13248–13253.

  • Drescher U. . 1997 Curr. Biol. 7: R799–R807.

  • Drescher U, Kremoser C, Handwerker C, Loschinger J, Noda M and Bonhoeffer F. . 1995 Cell 82: 359–370.

  • Easty DJ, Guthrie BA, Maung K, Farr CJ, Lindberg RA, Toso RJ, Herlyn M and Bennett DC. . 1995 Cancer Res. 55: 2528–2532.

  • Easty DJ, Hill SP, Hsu MY, Fallowfield ME, Florenes VA, Herlyn M and Bennett DC. . 1999 Int. J. Cancer 84: 494–501.

  • Eph-Nomenclature-Committee.1997 Cell 90: 403–404.

  • Feldheim DA, Vanderhaeghen P, Hansen MJ, Frisen J, Lu Q, Barbacid M and Flanagan JG. . 1998 Neuron 21: 1303–1313.

  • Flanagan JG and Vanderhaeghen P. . 1998 Annu. Rev. Neurosci. 21: 309–345.

  • Flenniken AM, Gale NW, Yancopoulos GD and Wilkinson DG. . 1996 Dev. Biol. 179: 382–401.

  • Folkman J. . 1995 Nat. Med. 1: 27–31.

  • Frisen J, Yates PA, McLaughlin T, Friedman GC, O'Leary DD and Barbacid M. . 1998 Neuron 20: 235–243.

  • Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, Pawson T, Davis S and Yancopoulos GD. . 1996 Neuron 17: 9–19.

  • Gerety SS, Wang HU, Chen ZF and Anderson DJ. . 1999 Mol. Cell. 4: 403–414.

  • Hanahan D, Christofori G, Naik P and Arbeit J. . 1996 Eur. J. Cancer 32A: 2386–2393.

  • Henkemeyer M, Orioli D, Henderson JT, Saxton TM, Roder J, Pawson T and Klein R. . 1996 Cell 86: 35–46.

  • Hirai H, Maru Y, Hagiwara K, Nishida J and Takaku F. . 1987 Science 238: 1717–1720.

  • Hock B, Bohme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, Holland S, Pawson T, Rubsamen-Waigmann H and Strebhardt K. . 1998 Proc. Natl. Acad. Sci. USA 95: 9779–9784.

  • Holland SJ, Gale NW, Mbamalu G, Yancopoulos GD, Henkemeyer M and Pawson T. . 1996 Nature 383: 722–725.

  • Holzman LB, Marks RM and Dixit VM. . 1990 Mol. Cell. Biol. 10: 5830–5838.

  • Huynh-Do U, Stein E, Lane AA, Liu H, Cerretti DP and Daniel TO. . 1999 EMBO J. 18: 2165–2173.

  • Imondi R, Wideman C and Kaprielian Z. . 2000 Development 127: 1397–1410.

  • Jones TL, Chong LD, Kim J, Xu RH, Kung HF and Daar IO. . 1998 Proc. Natl. Acad. Sci. USA 95: 576–581.

  • Kalo MS and Pasquale EB. . 1999 Cell Tissue Res. 298: 1–9.

  • Kiyokawa E, Takai S, Tanaka M, Iwase T, Suzuki M, Xiang YY, Naito Y, Yamada K, Sugimura H and Kino I. . 1994 Cancer Res. 54: 3645–3650.

  • Labrador JP, Brambilla R and Klein R. . 1997 EMBO J. 16: 3889–3897.

  • Lin D, Gish GD, Songyang Z and Pawson T. . 1999 J. Biol. Chem. 274: 3726–3733.

  • Linnemann T, Geyer M, Jaitner BK, Block C, Kalbitzer HR, Wittinghofer A and Herrmann C. . 1999 J. Biol. Chem. 274: 13556–13562.

  • Mackay DJ and Hall A. . 1998 J. Biol. Chem. 273: 20685–20688.

  • Maru Y, Hirai H and Takaku F. . 1990 Oncogene 5: 445–447.

  • Maru Y, Hirai H, Yoshida MC and Takaku F. . 1988 Mol. Cell. Biol. 8: 3770–3776.

  • McBride JL and Ruiz JC. . 1998 Mech. Dev. 77: 201–204.

  • Mellitzer G, Xu QL and Wilkinson DG. . 1999 Nature 400: 77–81.

  • Miao H, Burnett E, Kinch M, Simon E and Wang BC. . 2000 Nature Cell. Biol. 2: 62–69.

  • Monschau B, Kremoser C, Ohta K, Tanaka H, Kaneko T, Yamada T, Handwerker C, Hornberger MR, Loschinger J, Pasquale EB, Siever DA, Verderame MF, Muller BK, Bonhoeffer F and Drescher U. . 1997 EMBO J. 16: 1258–1267.

  • Nakamoto M, Cheng HJ, Friedman GC, McLaughlin T, Hansen MJ, Yoon CH, O'Leary DD and Flanagan JG. . 1996 Cell 86: 755–766.

  • Nikolova Z, Djonov V, Zuercher G, Andres AC and Ziemiecki A. . 1998 J. Cell. Sci. 111: 2741–2751.

  • Orioli D, Henkemeyer M, Lemke G, Klein R and Pawson T. . 1996 EMBO J. 15: 6035–6049.

  • Orsulic S and Kemler R. . 2000 J. Cell. Sci. 113: 1793–1802.

  • Pandey A, Lindberg RA and Dixit VM. . 1995a Curr. Biol. 5: 986–989.

  • Pandey A, Shao H, Marks RM, Polverini PJ and Dixit VM. . 1995b Science 268: 567–569.

  • Pasquale EB. . 1997 Curr. Opin. Cell Biol. 9: 608–615.

  • Smith A, Robinson V, Patel K and Wilkinson DG. . 1997 Curr. Biol. 7: 561–570.

  • Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL and Daniel TO. . 1998 Genes Dev. 12: 667–678.

  • Takahashi H and Ikeda T. . 1995 Oncogene 11: 879–883.

  • Torres R, Firestein BL, Dong H, Staudinger J, Olson EN, Huganir RL, Bredt DS, Gale NW and Yancopoulos GD. . 1998 Neuron 21: 1453–1463.

  • Vanderhaeghen P, Lu Q, Prakash N, Frisen J, Walsh CA, Frostig RD and Flanagan JG. . 2000 Nat. Neurosci. 3: 358–365.

  • Vogt T, Stolz W, Welsh J, Jung B, Kerbel RS, Kobayashi H, Landthaler M and McClelland M. . 1998 Clin. Cancer Res. 4: 791–797.

  • Wahl S, Barth H, Ciossek T, Aktories K and Mueller BK. . 2000 J. Cell. Biol. 149: 263–270.

  • Wang HU, Chen ZF and Anderson DJ. . 1998 Cell 93: 741–753.

  • Wicks IP, Wilkinson D, Salvaris E and Boyd AW. . 1992 Proc. Natl. Acad. Sci. USA 89: 1611–1615.

  • Winning RS, Scales JB and Sargent TD. . 1996 Dev. Biol. 179: 309–319.

  • Xu Q, Alldus G, Holder N and Wilkinson DG. . 1995 Development 121: 4005–4016.

  • Xu Q, Mellitzer G, Robinson V and Wilkinson DG. . 1999 Nature 399: 267–271.

  • Yancopoulos GD, Klagsbrun M and Folkman J. . 1998 Cell 93: 661–664.

  • Zantek ND, Azimi M, Fedor-Chaiken M, Wang B, Brackenbury R and Kinch MS. . 1999 Cell Growth Differ. 10: 629–638.

  • Zhang JH, Cerretti DP, Yu T, Flanagan JG and Zhou R. . 1996 J. Neurosci. 16: 7182–7192.

  • Zisch AH, Stallcup WB, Chong LD, Dahlin-Huppe K, Voshol J, Schachner M and Pasquale EB. . 1997 J. Neurosci. Res. 47: 655–665.

  • Zohn IM, Campbell SL, Khosravi-Far R, Rossman KL and Der CJ. . 1998 Oncogene 17: 1415–1438.

  • Zou JX, Wang B, Kalo MS, Zisch AH, Pasquale EB and Ruoslahti E. . 1999 Proc. Natl. Acad. Sci. USA 96: 13813–13818.

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Acknowledgements

The authors' work is supported by grants from the NIH (to EB Pasquale), the University of California Breast Cancer Program (EB Pasquale), and the National Sciences and Engineering Research Council of Canada (to VC Dodelet).

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  1. The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, California, CA, USA

    Vincent C Dodelet & Elena B Pasquale

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Dodelet, V., Pasquale, E. Eph receptors and ephrin ligands: embryogenesis to tumorigenesis. Oncogene 19, 5614–5619 (2000). https://doi.org/10.1038/sj.onc.1203856

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