Signal transduction in hamster fibroblasts overexpressing the human EGF receptor

Human EGF receptors (HERs) were expressed in CCL39 hamster fibroblasts, a cell line responding only weakly to EGF despite the presence of 10-20,000 EGF receptors per cell. High expression of HERs (800,000 per cell) conferred EGF responsiveness. In these cells EGF is a potent mitogen, induces strong receptor autophosphorylation, phosphorylation of cellular substrates on tyrosine, activates the Na+/H+ exchanger, and weakly stimulates phosphoinositide (PI) turnover. Activation of PI turnover by a mitogen activating a receptor tyrosine kinase has not been observed previously in CCL39 cells. We present evidence, however, that the activation of this signaling pathway which is insensitive to pertussis toxin does not mediate the proliferative response. Unlike NIH 3T3 cells, CCL39 fibroblasts overexpressing HERs are not transformed nor can a transformed phenotype be observed in response to EGF or TGF alpha.