Meta-Biol

• Pathways

While the roles of EGFR and EPS15 phosphorylation and ubiquitination are not completely clear, recent evidence supports the idea that EGFR-mediated phosphorylation of EPS15 promotes the clustering of the activated receptor into clathrin-coated pits, while the dephosphorylated EPS15 targets EGFR for endocytosis through a caveolin-and lipid raft-dependent route (reviewed in van Bergen en Henegouwen, 2009). Consistent with this, overexpression of the phosphatase PTPN3, which dephosphorylates EPS15 in vitro and in vivo, promotes the internalization of EGFR into caveolin-enriched structures and targets it for lysosomal degradation (Li et al, 2015).