Fig. 1. Constitutive recycling and induced endocytosis of EGFR and their inhibition by EphA-ephrinA.

(A) In addition to endocytosis and degradation of EGF-stimulated EGFR that is tyrosine phosphorylated (P) and ubiquitinated (U), Stallaert et al. report a constitutive recycling mechanism of the ligand-free EGFR. The recycling maintains EGFR abundance at the PM. Both pathways depend on Akt. EphA-ephrinA interactions upon cell-cell contact inhibit Akt and suppress EGFR recycling. (B) In the absence of cell-cell contact, such as at the leading edge of migrating cells, the lack of EphA-ephrinA engagement unleashes Akt activation and promotes both recycling and endocytosis of EGFR, which can be further enhanced by increased EGF levels during wound healing and metastasis.