Figure 11.

Model of EGFR endocytosis during mitosis. In interphase cells, low EGF doses (>2 ng/mL) only activate clathrin-mediated endocytosis (CME), leading to receptor recycling. High EGF doses (>20 ng/mL) also activate CME, but can also activate non-clathrin-mediated endocytosis (NCE) due to the dose-dependent activation of CBL and EGFR ubiquitination. NCE leads to lysosomal degradation of EGFR. In mitotic cells, CME is shut off. Therefore, EGFR endocytosis must proceed by NCE. Both low and high concentrations of EGF activate NCE during mitosis, and this may be because contrary to interphase cells, low EGF concentrations can activate CBL and EGFR ubiquitination. Therefore, mitotic EGFR endocytosis likely leads exclusively to lysosomal degradation.