Proteolytic processing of epidermal growth factor within endosomes.

Following binding to its plasma membrane receptor, epidermal growth factor is transferred into three biochemically distinct endosomal compartments in a temporal fashion prior to delivery to the lysosomes. During this migration, the ligand undergoes sequential proteolytic processing resulting in the removal of six amino acid residues from the carboxy terminus. Individual events in the processing occur in different endosomal compartments. Incubations conducted in the presence of methylamine result in the retention of the ligand in an early endosomal compartment and processing is limited to the removal of the carboxy terminal arginine residue. This identification of specific processed forms of radiolabeled epidermal growth factor within distinct endosomal compartments demonstrates the compartmentalization of the presumed proteases which may serve as biochemical markers for these endosomal populations.