The endocytosis of gp185erbB-2 was studied using chimeric receptors in which the intracellular domain of erbB-2, or subdomins thereof, was substituted for the corresponding regions of the epidermal growth factor (EGF) receptor. Chimeric and wild-type EGF or erbB-2 receptors were expressed in mouse NIH3T3 or NR6 fibroblasts and in a human mammary adenocarcinoma cell line, MDAMB-134. The rate of EGF-induced internalization for the chimera consisting of the extracellular EGF receptor domain and intracellular erbB-2 domain was reduced three- to fourfold compared with the wild-type EGF receptor. The low rate of internalization of the chimeric receptor resulted in impaired down-regulation and degradation of the receptor. Substitution of the carboxyl terminus of erbB-2 for the corresponding region of the EGF receptor caused a similar decrease of receptor endocytosis, whereas substitution of the erbB-2 tyrosine kinase domain did not affect internalization and down-regulation. Since the tyrosine kinase of the internalization-defective chimeric receptors could be activated by EGF, kinase activity and autophosphorylation of erbB-2 do not appear to be sufficient for a maximum rapid internalization of the chimeric receptors. These results suggest that the carboxyl terminus of erbB-2 either does not possess all the signals required for the rapid internalization or contains an inhibitory signal for rapid internalization.
|Titolo:||The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired|
DI FIORE, PIER PAOLO (Secondo)
|Parole Chiave:||Animals; Dose-Response Relationship, Drug; Receptor, Epidermal Growth Factor; Receptor, erbB-2; Epidermal Growth Factor; Humans; Amino Acid Sequence; Mice; Recombinant Fusion Proteins; Proto-Oncogene Proteins; Down-Regulation; Molecular Sequence Data; Cell Line|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||nov-1993|
|Appare nelle tipologie:||01 - Articolo su periodico|