Abstract
Epidermal growth factor (EGF), which can be purified from the mouse submaxillary gland1 or from pregnant human urine2, is a potent multiplication-stimulating factor for several types of cultured cells, including human fibroblasts2,3 and glial cells4. The molecule binds with high affinity and saturation kinetics to a cell-surface receptor3, is subsequently internalised5,7 and finally degraded5,6. The binding event is accompanied by a reduction in the number of EGF receptors5,8. This phenomenon—‘receptor down-regulation’—has been demonstrated with several hormones and may be a general principle for the modulation of binding groups on the outer cell surface9,10. Further, it has been proposed that receptor loss acts to regulate the cellular response to the binding ligand11. The present study provides direct experimental support for this hypothesis. It demonstrates that down-regulation of EGF receptors on glial cells causes desensitisation of the mitogenic response of these cells to subsequent stimulation with EGF.
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References
Cohen, S. J. biol. Chem. 237, 1555–1562 (1962).
Cohen, S. & Carpenter, G. Proc. natn. Acad. Sci. U.S.A. 72, 1317–1321 (1975).
Hollenberg, M. D. & Cuatrecasas, P. Proc. natn. Acad. Sci. U.S.A. 70, 2964–2968 (1973).
Westermark, B. Biochem. biophys. Res. Commun. 69, 304–310 (1976).
Carpenter, G., Lembach, K.J., Morrison, M.M. & Cohen, S. J. biol. Chem. 250, 4297–4304 (1975).
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).
Aharanov, A., Pruss, R. M. & Herschman, H. R. J. biol. Chem. 253, 3970–3977 (1978).
Raff, M. Nature 259, 265–266 (1976).
Roth, J. et al. Recent Prog. Horm. Res. 31, 95–139 (1975).
Gavin, J. R., Roth, J., Neville, D. M. Jr., de Meyts, P. & Buell, D. N. Proc. natn. Acad. Sci. U.S.A. 71, 84–88 (1974).
Scatchard, G. Ann. N.Y. Acad. Sci. 51, 660–672 (1949).
Westermark, B. Proc. natn. Acad. Sci. U.S.A. 74, 1619–1621 (1977).
Livingstone, J. N., Purvis, B. J. & Lockwood, D. H. Nature 273, 394–396 (1978).
Tsuruhara, T., Dufau, M. L., Cigorraga, S. & Catt, K. J. J. biol. Chem. 252, 9002–9009 (1977).
Pontén, J., Westermark, B. & Hugosson, R. Expl Cell Res. 58, 393–400 (1969).
Lindgren, A., Westermark, B. & Pontén, J., Expl. Cell Res. 95, 311–319 (1975).
Heldin, C.-H., Westermark, B. & Wasteson, Å. Expl. Cell Res. 109, 429–437 (1977).
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Heldin, CH., Westermark, B. & Wasteson, Å. Desensitisation of cultured glial cells to epidermal growth factor by receptor down-regulation. Nature 282, 419–420 (1979). https://doi.org/10.1038/282419a0
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DOI: https://doi.org/10.1038/282419a0
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