The biochemistry and physiology of the receptor-kinase for epidermal growth factor

Epidermal growth factor (EGF) is a polypeptide mitogen that stimulates the proliferation of epidermal and epithelial cells in intact animals and a variety of cell types in cell culture. The biological effects of EGF are mediated by a 170000 dalton receptor located in the plasma membrane. Studies with cultured cells and more recently with subcellular membrane preparations have revealed significant information about the mechanism of action of EGF. In particular, events which occur immediately upon the formation of hormone-receptor complexes have been described. The biochemical signaling that must occur between the membrane-localized EGF-receptor complexes and the cell nucleus to initiate replicative DNA synthesis appears to involve an initial phosphorylation step. The EGF receptor molecule contains a protein kinase active site and this kinase activity is enhanced by EGF binding. Since the kinase phosphorylates tyrosyl residues, this normal growth-regulating system bears a similarity to the mechanism employed by certain oncogenic viruses to transform normal cellular growth behavior.