作者: Z Fan , J Mendelsohn , H Masui , R Kumar
DOI: 10.1016/S0021-9258(19)36895-4
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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.