Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity.

作者: G N Gill , T Kawamoto , C Cochet , A Le , J D Sato

DOI: 10.1016/S0021-9258(17)42857-2

关键词:

摘要: Four mouse monoclonal antibodies specific for human epidermal growth factor (EGF) receptors have been prepared using EGF receptor protein from A431 epidermoid carcinoma cells as immunogen. We determined the effect of these on two known functions receptor: binding and tyrosine kinase. Three (225, 528, 579) are inhibitors binding, whereas fourth (455) does not compete but immunoprecipitates receptor. Inhibition is mixed competitive noncompetitive type. The three competing antagonists EGF-stimulated kinase activity assayed both in intact an exogenous peptide substrate solubilized membranes. These immunoglobulins partial agonists self-phosphorylation membranes exhibit only antagonist this reaction cells. recognize variant with same efficiency parental Such can be used to control concentration which activated by EGF.

参考文章(29)
D Thom, A J Powell, C W Lloyd, D A Rees, Rapid isolation of plasma membranes in high yield from cultured fibroblasts Biochemical Journal. ,vol. 168, pp. 187- 194 ,(1977) , 10.1042/BJ1680187
G. H. Sato, J. Mendelsohn, J. Polikoff, J. D. Sato, A. D. Le, T. Kawamoto, Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Molecular biology & medicine. ,vol. 1, pp. 511- 529 ,(1983)
C. Richard Savage, Stanley Cohen, Epidermal Growth Factor and a New Derivative Journal of Biological Chemistry. ,vol. 247, pp. 7609- 7611 ,(1972) , 10.1016/S0021-9258(19)44568-7
A B Schreiber, T A Libermann, I Lax, Y Yarden, J Schlessinger, Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. Journal of Biological Chemistry. ,vol. 258, pp. 846- 853 ,(1983) , 10.1016/S0021-9258(18)33127-2
S. Cohen, H. Ushiro, C. Stoscheck, M. Chinkers, A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. Journal of Biological Chemistry. ,vol. 257, pp. 1523- 1531 ,(1982) , 10.1016/S0021-9258(19)68224-4
C Erneux, S Cohen, D L Garbers, The kinetics of tyrosine phosphorylation by the purified epidermal growth factor receptor kinase of A-431 cells. Journal of Biological Chemistry. ,vol. 258, pp. 4137- 4142 ,(1983) , 10.1016/S0021-9258(18)32595-X
N D Richert, M C Willingham, I Pastan, Epidermal growth factor receptor. Characterization of a monoclonal antibody specific for the receptor of A431 cells. Journal of Biological Chemistry. ,vol. 258, pp. 8902- 8907 ,(1983) , 10.1016/S0021-9258(18)32142-2