Regulation of epidermal growth factor receptor in NIH3T3/HER14 cells by antireceptor monoclonal antibodies.

作者: Z Fan , J Mendelsohn , H Masui , R Kumar

DOI: 10.1016/S0021-9258(19)36895-4

关键词:

摘要: The mechanism(s) by which monoclonal antibodies (mAbs) against the epidermal growth factor (EGF) receptor regulate function have been investigated with NIH3T3/HER14 fibroblasts expressing human EGF receptors. Bivalent 225 mAb or monovalent Fab' inhibited transforming (TGF)-alpha-induced tyrosine phosphorylation and cell proliferation. Culture of HER14 cells did not activate kinase when assayed after lysis in SDS sample buffer. However, were cultured bivalent mAb, but Fab', subsequently lysed further incubated Triton X-100 buffer containing proteinase phosphatase inhibitors, was observed. Phosphorylation confined to residues addition genistein lysis, indicating that it due activation protein kinase. activity unphysiologic, contrast TGF-alpha, occurred only delayed kinetics; serine threonine occur; down-regulation receptors slower. Selective mAb-mediated on sufficient a SH2 group-bearing substrate, phospholipase C-gamma, serine/threonine is required for activity. These studies provide novel insights into capacity modulate function.

参考文章(42)
M Torti, K.B. Marti, D Altschuler, K Yamamoto, E.G. Lapetina, Erythropoietin induces p21ras activation and p120GAP tyrosine phosphorylation in human erythroleukemia cells. Journal of Biological Chemistry. ,vol. 267, pp. 8293- 8298 ,(1992) , 10.1016/S0021-9258(18)42441-6
M Spaargaren, L H Defize, J Boonstra, S W de Laat, Antibody-induced dimerization activates the epidermal growth factor receptor tyrosine kinase. Journal of Biological Chemistry. ,vol. 266, pp. 1733- 1739 ,(1991) , 10.1016/S0021-9258(18)52357-7
S. Demignot, M.C. Garnett, R.W. Baldwin, Mouse IgG2b monoclonal antibody fragmentation. Preparation and purification of Fab, Fc and Fab/c fragments. Journal of Immunological Methods. ,vol. 121, pp. 209- 217 ,(1989) , 10.1016/0022-1759(89)90162-2
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
Ulrich Rodeck, Carla Molthoff, Meenhard Herlyn, Michael Varello, Dorothee Herlyn, Zenon Steplewski, Barbara Atkinson, Hilary Koprowski, Tumor Growth Modulation by a Monoclonal Antibody to the Epidermal Growth Factor Receptor: Immunologically Mediated and Effector Cell-independent Effects Cancer Research. ,vol. 47, pp. 3692- 3696 ,(1987)