Surface distribution and internalization of erbB-2 proteins.
We report the localization over the cell surface and the early steps of antibody-induced internalization of the product of the erbB-2 proto-oncogene, structurally related to the epidermal growth factor receptor (EGFR). We show that erbB-2/p 185 is mostly excluded from endocytic pits on the cell surface. Incubation at 37 degrees C with an anti-erbB-2/p185 monoclonal antibody induces the rapid entry of the protein into the cell. Similar internalization is shown by a chimeric molecule EGFR/erbB-2 in response to EGF. Both the timing and the pathway of internalization followed by the erbB-2/p185 appear totally similar to those described for the EGFR. At variance with the normal erbB-2/p185, two mutant activated erbB-2 proteins are frequently localized within endocytic pits of the cell surface, indicating that mutations in the transmembrane regions may determine constitutive internalization of the protein.
Istituto Nazionale Ricerca sul Cancro di Genova, Sezione di Biotecnologie, Rome, Italy.
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D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051379:Mice; D016296:Mutagenesis; D010587:Phagocytosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins