Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors

TPA (12-O-tetradecanoyl-phorbol-13-acetate) reversibly inhibits the binding of (125)I-labelled epidermal growth factor (EGF) to treated mouse and human cells, but does not affect the binding of various other ligands to their membrane receptors. It alters the affinity of the receptors for EGF without changing the total number of available receptors per cell. Those phorbol esters which stimulate cell growth in culture and have tumour-promoting activity in vivo alter the EGF-receptor affinity, while the biologically inactive derivatives fail to change the affinity of EGF for its receptors.