The Epidermal Growth Factor Receptor; Studies in Cultured Hepatocytes and During Liver Regeneration

Abstract

Epidermal growth factor is a mitogen for a broad range of cell types [1]. Infusion of EGF in intact rats induces hepatic DNA synthesis [2]; similar results are seen when EGF is incubated with primary cultures of rat hepatcoytes [3]. To determine whether EGF plays a role in the physiologic regulation of growth we have begun a series of studies of EGF-EGF receptor interaction during the course of liver regeneration and in primary cultures of hepatocytes. EGF transduces its signal by binding to a 170,000 molecular weight transmembrane glycoprotein. The binding of EGF leads to receptor clustering and internalization [4, 5]. The EGF receptor contains a ligand stimulated protein kinase activity located on the cytoplasmic side. This intrinsic kinase phosphorylates tyrosine residues, an enzymatic activity analogous to other growth factor receptors and oncogene products [6]. The binding of EGF activates the tyrosine kinase activity in vitro [6, 7]. However, the nature and localization of the critical substrates is unknown.