Abstract
EPIDERMAL GROWTH FACTOR (EGF), a potent polypeptide mitogen, has been studied intensively by those concerned with the molecular events leading to cell proliferation1–4. The initial, reversible interaction of EGF with a specific cell surface receptor and the subsequent internalisation and degradation of EGF, and by inference the EGF–receptor complex, are well documented, although the role of these events in mitogenesis is unknown4–6. In an attempt to define this role, we used photoaffinity probes to specifically cross-link radiolabelled EGF to its receptor, a 185,000-dalton polypeptide on the surface of murine 3T3 cells7. These probes also enabled us to follow the metabolic fate of this receptor8. We have since noted that a small portion of the underivatised radiolabelled EGF that binds specifically to 3T3 cells or isolated 3T3 cell membranes becomes directly and irreversibly linked to a polypeptide of molecular weight (MW) 185,000. Here, we document this association and show that the resulting complex has properties identical to those of the EGF-receptor complex originally identified by photoaffinity labelling.
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References
Diamond, I., Legg, A., Schneider, J. A. & Rosengurt, E. J. biol. Chem. 253, 866–871 (1978).
Holley, R. W., Armour, R., Baldwin, J. H., Brown, K. D. & Yeh, Y.-C. Proc. natn. Acad. Sci. U.S.A. 74, 5046–5050 (1977).
Aharonov, A., Pruss, R. M. & Herschman, H. R. J. biol. Chem. 253, 3970–3977 (1978).
Carpenter, G. & Cohen, S. J. Cell Biol. 71, 159–171 (1976).
Haigler, H., Ash, J. F., Singer, S. J. & Cohen, S. Proc. natn. Acad. Sci. U.S.A. 75, 3317–3321 (1978).
Schlessinger, J., Schechter, Y., Willingham, M. C. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 75, 2659–2663 (1978).
Das, M. et al. Proc. natn. Acad. Sci. U.S.A. 74, 2790–2794 (1977).
Das, M. & Fox, C. F. Proc. natn. Acad. Sci. U.S.A. 75, 2644–2648 (1978).
Trouet, A. & Tulkens, P. in Membranes and Disease (eds Bollis, L., Hoffman, J. F. & Leaf, A.) 131–144 (Raven, New York, 1976).
Siefring, G. E., Apostol, A. B., Velasco, P. T. & Lorand, L. Biochemistry 17, 2598–2604 (1978).
Laemmli, V. K. Nature 277, 680–685 (1970).
Fahey, J. L. in Methods in Immunology and Immunochemistry (ed. Williams, C.) 321–322 (Academic, New York, 1967).
Bygny, R. L., Orth, O. N. & Cohen, S. Endocrinology 90, 1261–1266 (1972).
Kessler, S. W. J. Immun. 115, 1617–1624 (1975).
Scatchard, G. Ann N.Y. Acad. Sci. 51, 660–672 (1949).
Schimmel, S. D., Kent, C., Bischoff, R. & Vagelos, P. R. Proc. natn. Acad. Sci. U.S.A. 70, 3195–3199 (1973).
Heitzman, H. & Richards, F. M. Proc. natn. Acad. Sci. U.S.A. 71, 3537–3541 (1974).
Fabricant, R. N., DeLarco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 74, 565–569 (1977).
Baker, J. B., Simmer, R. L., Glenn, K. C. & Cunningham, D. D. Nature 278, 743–745 (1979).
Kahn, C. R. & Baird, K. J. biol. Chem. 253, 4900–4906 (1978).
Green, H. & Kehinke, O. Cell 13 19–37.
Schechter, Y., Hernaez, L. & Cuatrecasas, P. Proc. natn. Acad. Sci. U.S.A. 75, 5788–5791 (1978).
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LINSLEY, P., BLIFELD, C., WRANN, M. et al. Direct linkage of epidermal growth factor to its receptor. Nature 278, 745–748 (1979). https://doi.org/10.1038/278745a0
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DOI: https://doi.org/10.1038/278745a0
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