title: The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane.
abstract: By constructing stably transfected cells harboring the same amount of epidermal growth factor (EGF) receptor (EGFR), but with increasing overexpression of ErbB2, we have demonstrated that ErbB2 efficiently inhibits internalization of ligand-bound EGFR. Apparently, ErbB2 inhibits internalization of EGF-bound EGFR by constitutively driving EGFR-ErbB2 hetero/oligomerization. We have demonstrated that ErbB2 does not inhibit phosphorylation or ubiquitination of the EGFR. Our data further indicate that the endocytosis deficiency of ErbB2 and of EGFR-ErbB2 heterodimers/oligomers cannot be explained by anchoring of ErbB2 to PDZ-containing proteins such as Erbin. Instead, we demonstrate that in contrast to EGFR homodimers, which are capable of inducing new clathrin-coated pits in serum-starved cells upon incubation with EGF, clathrin-coated pits are not induced upon activation of EGFR-ErbB2 heterodimers/oligomers.
authors.affiliation: Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Haslekås
authors.forename: Kamilla
authors.initials: K
authors.lastname: Breen
authors.forename: Ketil W
authors.initials: KW
authors.lastname: Pedersen
authors.forename: Lene E
authors.initials: LE
authors.lastname: Johannessen
authors.forename: Espen
authors.initials: E
authors.lastname: Stang
authors.forename: Inger Helene
authors.initials: IH
authors.lastname: Madshus
mesh_terms: D000818:Animals; D001011:Aorta; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D022163:Clathrin-Coated Vesicles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D013552:Swine
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases