Figure 3

Possible role of the Eps15 proteins in intracellular trafficking of EGFR. EGFRs are partly present in caveolae and are released from these structures upon activation. Phosphorylated EGFRs become ubiquitinated by the action of Cbl and are trapped by Eps15 in either the clathrin-coated vesicle (CCV) route or clathrin-independent route (Ci). Eps15 is associated to the ubiquitinated EGFR via its UIMs and to α-adaptin in the AP-2-complex in the CCV, and to a putative adaptor protein (?) at the clathrin independent pit. Eps15b is found at the early endosome (EE) in a tri-complex with STAM and Hrs bound to the clathrin-coated sheet. Inactive EGFRs are recycled back to the plasma membrane while active receptors are packed in multi vesicular vesicles (MVB) by the actions of the ESCRT-0, -I, -II, and -III complexes and degraded in lysosomes.