Epidermal growth factor action as a model for lymphokine function.

The experimental findings described here represent a general approach toward understanding the mechanism of action of polypeptide hormones and mediators by using epidermal growth factor (EGF) as the model system. A photoaffinity labeling method was used for identifying the cell-surface EGF receptor and for following its dynamic and migratory fate after binding to EGF. A different approach involving receptor insertion revealed that the EGF receptor can be transferred in a biologically active orientation from donor hepatic membranes to recipient receptor-negative mutant cells by a novel mechanism requiring no added fusogenic agent. These studies of the EGF receptor led us to probe into the transduction mechanism that relates hormone-receptor binding to its biological function. EGF-receptor interaction in responsive cells was shown to lead to the intracellular generation of macromolecular protein activators of nuclear DNA replication. These molecular intermediates lead to the generation of an ultimate committed prereplicative state that is an innate characteristic and a global property of the whole cell. These studies of the EGF receptor and EGF-induced internal events serve to illustrate the types of systems that might be explored in future research on lymphokines and other such biologically relevant mediators of mitogenesis.