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. 1995 Sep 12;92(19):8719–8723. doi: 10.1073/pnas.92.19.8719

Ligand-induced endocytosis of epidermal growth factor receptors that are defective in binding adaptor proteins.

A Nesterov 1, H S Wiley 1, G N Gill 1
PMCID: PMC41038  PMID: 7568004

Abstract

Ligand-activated epidermal growth factor receptors (EGFRs) associate with coated pit adaptor proteins (AP2) in vivo, implying a mechanism for receptor retention in coated pits during internalization. Using an in vitro binding assay, we localized the adaptor binding determinant to residues 970-991 of EGFRs and confirmed specificity by competition with a synthetic peptide corresponding to this sequence. A mutant EGFR lacking this AP2 binding determinant did not associate with AP2 in vivo but demonstrated internalization and down-regulation kinetics indistinguishable from its wild-type counterpart. Immunocytochemistry confirmed ligand-induced internalization of the mutant EGFR. These data suggest that endocytic determinants are distinct from AP2 binding determinants and that processes other than association with AP2 regulate endocytosis of EGFRs.

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