EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake

Epidermal growth factor (EGF) binding to its receptor causes rapid phosphor ylation of the clathrin heavy chain at tyrosine 1477, which lies in a domai n controlling clathrin assembly. EGF-mediated clathrin phosphorylation is f ollowed by clathrin redistribution to the cell periphery and is the product of downstream activation of SRC kinase by EGF receptor (EGFR) signaling. I n cells lacking SRC kinase, or cells treated with a specific SRC family kin ase inhibitor, EGF stimulation of clathrin phosphorylation and redistributi on does not occur, and EGF endocytosis is delayed. These observations demon strate a role for SRC kinase in modification and recruitment of clathrin du ring ligand-induced EGFR endocytosis and thereby define a novel effector me chanism for regulation of endocytosis by receptor signaling.