Model for differential EGFR regulation by CD and GEEC endocytosis.

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Model for differential EGFR regulation by CD and GEEC endocytosis. Model for differential EGFR regulation by CD and GEEC endocytosis. At low doses of EGF, EGFR is largely internalized through CD endocytosis, which primarily results in receptor recycling and sustained signaling (Sigismund et al., 2008, 2005). At high doses of EGF, a substantial fraction of EGFR is internalized through Graf-dependent GEEC endocytosis, which primarily targets internalized receptors to degradation, causing signal attenuation. Under the latter condition, Cbl is recruited to and ubiquitylates phosphorylated EGFRs. This post-translational modification enhances physical interactions between EGFR and Graf to promote GEEC endocytosis of the receptor. CCV, clathrin-coated vesicle. Sungdae Kim et al. Development 2017;144:4159-4172 © 2017. Published by The Company of Biologists Ltd