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. Author manuscript; available in PMC: 2010 Jan 1.
Published in final edited form as: Annu Rev Biochem. 2009;78:435–475. doi: 10.1146/annurev.biochem.013008.092711

Figure 4.

Figure 4

An EGFR internalization model. Homodimerization and autophosphorylation of EGFR induced by EGF binding recruits and interacts with Cbl/CIN85 complex through the variant SH2 domain of Cbls. Cbls mediate the ubiquitination of EGFR and monoubiquitination of CIN85. EGFR/Cbl/CIN85 with other monoubiquitinated endocytic proteins such as Eps15, Eps15R, epsins and Hrs travel from early endosomes to late endosomes and MVBs. Subsequent invagination of cargo proteins into the lumenal vesicles of MVBs targets MVBs for fusion with lysosomes and then final degradation of EGFR. A certain proportion of EGFR will be deubiquitinated by DUBs and recycled back to the cell membrane.