A COMPARISON OF EPIDERMAL GROWTH-FACTOR RECEPTOR-MEDIATED MITOGENIC SIGNALING IN RESPONSE TO TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMALGROWTH-FACTOR IN CULTURED FETAL-RAT HEPATOCYTES

We compared the ability of Epidermal Growth Factor (EGF) and Transform ing Growth Factor alpha (TGF alpha) to transduce a mitogenic signal vi a their common receptor, the EGF receptor, in primary cultures of feta l rat hepatocytes. Mitogenic potency, measured as DNA synthesis, was s imilar in response to EGF and TGF alpha although signal initiation, me asured as EGF receptor tyrosine phosphorylation, was more than 3-fold higher in response to EGF compared to TGF alpha. Downstream signal tra nsduction events including She tyrosine phosphorylation, Shc/Grb2 comp lex formation and MAP kinase activation were similar in response to EG F and TGF alpha, thus indicating a dissociation between potency for re ceptor activation versus signal propagation. These data suggest that T GF alpha may preferentially activate an EGF receptor population linked to the Ras/MAP kinase pathway. In contract, EGF shows no such selecti vity, thereby reducing the mitogenic potency of EGF relative to its ab ility to activate the EGF receptor.