Receptor internalization and the role of ubiquitin. The example shown here is that of the EGF receptor. An activated EGFR is ubiquitinated at the plasma membrane and recruits the endocytic adaptor proteins EPS15 and EPSIN-1. These are ubiquitinated, in turn, and direct the internalized receptor to the endosomal pathway where it binds the sorting protein HRS. This is also ubiquitinated and directs progression of the ubiquitinated receptors towards lysosomal degradation through the ESCRT complexes. For simplicity, the EGF receptor is depicted as monoubiquitinated: in reality, it is both multimono- and polyubiquitinated. MVB, multivesicular body.