Epidermal Growth Factor Receptor

A monoclonal antibody to the epidermal growth factor (EGF) receptor of A431 cells, denoted 2Dl-IgM, was generated after fusion of immunized BALB/c mouse spleen cells with SpZ/O-Ag14 myeloma cells, Specific binding of 2D1-IgM to the A431 cell-surface receptor for EGF was demonstrated by indirect immunofluorescence, immunoprecipitation, and immunoblot analysis. Scatchard analysis of lz6I-EGF binding to A431 cells demonstrated that ZDI-IgM treatment did not change the number of EGF receptors, but caused an increase in the affinity of EGF receptors from a population of low affinity to a uniform population of high affinity. Like EGF, ZD1-IgM induced phosphorylation of EGF receptors and EGF receptor clustering. As in the case of EGF, a biphasic growth response with stimulation of DNA synthesis at low and inhibition at high concentrations of ZD1-IgM was evident in A43 l cells. The intrinsic “EGF-like” bioactivity of 2D1-IgM was enhanced by the presence of EGF. These results suggest that (i) the binding of 2D1-IgM to the EGF receptor at a different site from that to which EGF binds can initiate an effective EGF-like biological response; and (ii) the EGF-like biological effects of PD1-IgM may be mediated by a population of high affinity EGF receptors which may be involved in the control of cellular growth.