Dimerization Activates the Epidermal Growth Factor Receptor Tyrosine Kinase

  • Marcel Spaargaren
  • Libert H. K. Defize
  • Johannes Boonstra
  • Siegfried W. de Laat
Conference paper
Part of the NATO ASI Series book series (volume 52)


The epidermal growth factor receptor (EGF-R) is a transmembrane glycoprotein of 170 kDa with an extracellular ligand binding domain, a single hydrophobic transmembrane stretch, and an intracellular domain containing protein tyrosine kinase activity (Ullrich et al., 1984). Binding of EGF to its receptor enhances this tyrosine kinase activity, thus inducing tyrosine phosphorylation of several protein substrates including the EGF-R itself (Hunter and Cooper, 1985). Activation of the EGF-R tyrosine kinase results in a cascade of biochemical and physiological responses, finally leading to stimulation of DNA synthesis and cell division in most cells (Carpenter, 1987). Using EGF-R mutants, the protein tyrosine kinase activity was shown to be essential for mitogenic signaling (Schlessinger, 1988a).


Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Mutant Epidermal Growth Factor Receptor Tyrosine Kinase Epidermal Growth Factor Receptor Activation Epidermal Growth Factor Receptor Phosphorylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Basu, A., Raghunath, M., Bishayee, S., and Das, M. (1989) Mol Cell. Biol. 9, 671–677.PubMedGoogle Scholar
  2. Basu, M., Sen-Majumdar, A., Basu, A., Murthy, U., and Das, M. (1986) J. Biol. Chem. 261, 12879–12882.PubMedGoogle Scholar
  3. Bertics, P.J., and Gill, G.N. (1985) J. Biol. Chem. 260, 14642–14647.PubMedGoogle Scholar
  4. Bishayee, S., Majumdar, S., Khire, J., and Das, M. (1989) J. Biol. Chem. 264, 11699–11705.PubMedGoogle Scholar
  5. Biswas, R., Basu, M., Sen-Majumdar, A., and Das, M. (1985) Biochemistry 24, 3795–3802.PubMedCrossRefGoogle Scholar
  6. Boni-Schnetzler, M., and Pilch, P.F. (1987) Proc. Natl. Acad. Sci. USA 84, 7832–7836.PubMedCrossRefGoogle Scholar
  7. Carpenter, G. (1987) Annu. Rev. Biochem. 56, 881–914.PubMedCrossRefGoogle Scholar
  8. Cochet, C., Kashles, O., Chambaz, E.M., Borello, I., King, C.R., and Schlessinger, J. (1989) J. Biol. Chem. 263, 3290–3295.Google Scholar
  9. Defize, L.H.K., Moolenaar, W.H., van der Saag, P.T., and de Laat, S.W. (1986) EMBO J. 5, 1187–1192.PubMedGoogle Scholar
  10. Defize, L.H.K., Mummery, C.L., Moolenaar, W.H., and de Laat, S.W. (1987) Cell Diff. 20, 87–102.CrossRefGoogle Scholar
  11. Defize, L.H.K., Boonstra, J., Meisenhelder, J., Kruijer, W., Tertoolen, L.G.J., Tilly, B.C., Hunter, T., van Bergen en Henegouwen, P.M.P., Moolenaar, W.H., and de Laat, S.W. (1989) J. Cell Biol. 109, 2495–2507.PubMedCrossRefGoogle Scholar
  12. Fanger, B.O., Austin, K.S., Earp, H.S., and Cidlowski, J.A. (1986) Biochemistry 25, 6414–6420.PubMedCrossRefGoogle Scholar
  13. Fanger, B.O., Stephens, J.E., and Staros, J.V. (1989) FASEB J. 3, 71–75.PubMedGoogle Scholar
  14. Gill, G.N., Kawamoto, T., Cochet, C., Le, A., Sato, J.D., Masui, H., McLeod, C., and Mendelsohn, J. (1984) J. Biol. Chem. 259, 7755–7760.PubMedGoogle Scholar
  15. Gill, G.N., Bertics, P.J., and Santon, J.B. (1987) Mol. Cell. Endocrinol. 51, 169–186.PubMedCrossRefGoogle Scholar
  16. Greenfield, C., Hiles, I., Waterfield, M.D., Federwisch, M., Wollmer, A., Blundell, T.L., and McDonald, N. (1989) EMBO J. 8, 4115–4123.PubMedGoogle Scholar
  17. Hammacher, A., Mellstrom, K., Heldin, C-H., and Westermark, B. (1989) EMBO J. 8, 2489–2495.PubMedGoogle Scholar
  18. Heldin, C-H., Ernlund, A., Rorsman, C., and Ronnstrand, L. (1989) J. Biol. Chem. 264, 8905–8912.PubMedGoogle Scholar
  19. Honegger, A.M., Kris, R.M., Ullrich, A., and Schlessinger, J. (1989) Proc. Natl. Acad. Sci. USA 86, 925–929.PubMedCrossRefGoogle Scholar
  20. Honegger, A.M., Schmidt, A., Ullrich, A., and Schlessinger, J. (1990) Mol. Cell. Biol. 10, 4035–4044.PubMedGoogle Scholar
  21. Hunter, T., and Cooper, J.A. (1985) Annu. Rev. Biochem. 54, 897–930.PubMedCrossRefGoogle Scholar
  22. Koland, J.G., and Cerione, R.A. (1988) J. Biol. Chem. 263, 2230–2237.PubMedGoogle Scholar
  23. Lyall, M., Zilberstein, A., Gazit, A., Gilon, C., Levitzki, A., and Schlessinger, J. (1989) J. Biol. Chem. 264, 14503–14509.PubMedGoogle Scholar
  24. Northwood, I.C., and Davis, R.J. (1988) J. Biol. Chem. 263, 7450–7453.PubMedGoogle Scholar
  25. O’Brien, R.M., Soos, M.A., and Siddle, K. (1987) EMBO J. 6, 4003–4010.PubMedGoogle Scholar
  26. Schlessinger, J. (1986) J. Cell Biol. 103, 2067–2072.PubMedCrossRefGoogle Scholar
  27. Schlessinger, J. (1988a) Biochemistry 27, 3119–3123.PubMedCrossRefGoogle Scholar
  28. Schlessinger, J. (1988b) Trends Biochem. Sci. 13, 443–447.PubMedCrossRefGoogle Scholar
  29. Schreiber, A.B., Lax, I., Yarden, Y., Eshhar, Z., and Schlessinger, J. (1981) Proc. Natl. Acad. Sci. USA 78, 7535–7539.PubMedCrossRefGoogle Scholar
  30. Schreiber, A.B., Libermann, T.A., Lax, I., Yarden, Y., and Schlessinger, J. (1983) J. Biol. Chem. 258, 846–853.PubMedGoogle Scholar
  31. Spaargaren, M., Defize, L.H.K., de Laat, S.W., and Boonstra, J. (1990) Biochem. Biophys. Res. Commun. 171, 882–889.PubMedCrossRefGoogle Scholar
  32. Spaargaren, M., Defize, L.H.K., Boonstra, J., and de Laat, S.W. (1991) J. Biol. Chem. 266, in press.Google Scholar
  33. Ullrich, A., Coussens, L., Hayflick, J.S., Dull, T.J., Gray, A., Tam, A.W., Lee, J., Yarden, Y., Libermann, T.A., Schlessinger, J., Downward, J., Mayes, E.L.V., Whittle, N, Waterfield, M.D., and Seeburg, P.H. (1984) Nature 309, 418–425.PubMedCrossRefGoogle Scholar
  34. Ullrich, A., and Schlessinger, J. (1990) Cell 61, 203–212.PubMedCrossRefGoogle Scholar
  35. Weber, W., Bertics, P.J., and Gill, G.N. (1984) J. Biol. Chem. 259, 14631–14636.PubMedGoogle Scholar
  36. Weiner, D.B., Liu, J., Cohen, J.A., Williams, W.V., and Greene, M.I. (1989) Nature 339, 230–231.PubMedCrossRefGoogle Scholar
  37. Yaish, P., Gazit, A., Gilon, C., and Levitzki, A. (1988) Science 242, 933–935.PubMedCrossRefGoogle Scholar
  38. Yarden, Y., and Schlessinger, J. (1987a) Biochemistry 26, 1434–1442.PubMedCrossRefGoogle Scholar
  39. Yarden, Y., and Schlessinger, J. (1987b) Biochemistry 26, 1443–1451.PubMedCrossRefGoogle Scholar
  40. Yarden, Y. (1990) Proc. Natl. Acad. Sci. USA 87, 2569–2573.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Marcel Spaargaren
    • 1
    • 2
  • Libert H. K. Defize
    • 1
  • Johannes Boonstra
    • 2
  • Siegfried W. de Laat
    • 1
  1. 1.Hubrecht LaboratoryNetherlands Institute for Developmental BiologyUtrechtThe Netherlands
  2. 2.Department of Molecular Cell BiologyUniversity of UtrechtUtrechtThe Netherlands

Personalised recommendations