Abstract
The epidermal growth factor (EGF) receptor is a tyrosine-specific protein kinase with autophosphorylating activity1–4. A 300 amino acid-long region of the receptor's cytoplasmic domain matches (35–90 % homology) sequences of transforming proteins from the src family5 and includes a putative nucleotide binding site6. Several of the src transforming proteins have tyrosine kinase activity7, but v-erb-B, which appears to be a truncated EGF receptor, is virtually identical to the receptor over this region and yet lacks detectable kinase activity8,9. To locate possible acceptor sites in the v-erb-B protein, we have mapped these sites in the human EGF receptor. We report here that three tyrosine sites near the C-terminus are phosphorylated in vitro. In intact cells, we find that EGF stimulates phosphorylation of several sites, the tyrosine 14 residues from the C-terminus being modified the most extensively. The equivalent site is absent in the v-erb-B protein of avian erythroblastosis virus (AEV) and may influence tyrosine kinase activity10,11.
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References
Cohen, S., Ushiro, H., Stoscheck, C. & Chinkers, M. J. biol. Chem. 257, 1523–1531 (1982).
Buhrow, S. A., Cohen, S. & Staros, J. V. J. biol. Chem. 257, 4019–4022 (1981).
Cohen, S., Fava, R. A. & Sawyer, S. T. Proc. natn. Acad. Sci. U.S.A. 79, 6237–6241 (1982).
Buhrow, S. A., Cohen, S., Garbers, D. L. & Staros, J. V. J. biol. Chem. 258, 7824–7827 (1983).
Ullrich, A. et al. Nature 309, 418–425 (1984).
Kamps, M. P., Taylor, S. S. & Sefton, B. M. Nature 310, 589–592 (1984).
Bishop, J. M. A. Rev. Biochem. 52, 301–354 (1983).
Hayman, M. J. et al. Cell 32, 579–588 (1983).
Privalsky, M. L. et al. Cell 32, 1257–1267 (1983).
Yamomoto, T. et al. Cell 35, 71–78 (1983).
Privalsky, M. L., Ralston, R. & Bishop, J. M. Proc. natn. Acad. Sci. U.S.A. 81, 704–707 (1984).
Downward, J. et al. Nature 307, 521–527 (1984).
Cassel, D., Pike, L. J., Grant, G. A., Krebs, E. G. & Glaser, L. J. biol. Chem. 258, 2945–2950 (1983).
Ushiro, H. & Cohen, S. J. biol. Chem. 255, 8363–8365 (1980).
Hunter, T. & Cooper, J. A. Cell 24, 741–752 (1981).
Hewick, R. M., Hunkapiller, M. W., Hood, L. E. & Dreyer, W. J. J. biol. Chem. 256, 7990–7997 (1981).
Waterfield, M. D., Scrace, G. & Totty, N. in Practical Protein Biochemistry (ed. Darbre, A.) (Wiley, New York, in the press).
Cooper, J A., Sefton, B. M. & Hunter, T. Meth. Enzym. 99, 387–402 (1983).
Smart, J. E. et al. Proc. natn. Acad. Sci. U.S.A. 76, 6013–6017 (1981).
Patschinsky, T., Hunter, T., Esch, F. S., Cooper, J. A. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 79, 973–977 (1982).
Hunter, T. & Cooper, J. A. UCLA Symp. molec. cell. Biol. 6, 360 (1983).
Fung, Y-K. T., Lewis, W. G., Crittenden, L. B. & Kung, H-J. Cell 33, 357–368 (1983).
Snyder, M. A., Bishop, J. M., Colby, W. W. & Levinson, A. D. Cell 32, 891–901 (1983).
Weinmaster, G., Zoller, M. J., Smith, M., Hinge, E. & Pawson, T. Cell 37, 559–568 (1984).
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Downward, J., Parker, P. & Waterfield, M. Autophosphorylation sites on the epidermal growth factor receptor. Nature 311, 483–485 (1984). https://doi.org/10.1038/311483a0
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DOI: https://doi.org/10.1038/311483a0
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