The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired

Alexander Sorkin, Pier Paolo Di Fiore, Graham Carpenter

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

The endocytosis of gp185erbB-2 was studied using chimeric receptors in which the intracellular domain of erbB-2, or subdomains 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.

Original languageEnglish
Pages (from-to)3021-3028
Number of pages8
JournalOncogene
Volume8
Issue number11
Publication statusPublished - Nov 1993

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Epidermal Growth Factor Receptor
Epidermal Growth Factor
Endocytosis
Down-Regulation
TYK2 Kinase
ErbB-2 Receptor
Protein-Tyrosine Kinases
Adenocarcinoma
Breast
Phosphotransferases
Fibroblasts
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired. / Sorkin, Alexander; Di Fiore, Pier Paolo; Carpenter, Graham.

In: Oncogene, Vol. 8, No. 11, 11.1993, p. 3021-3028.

Research output: Contribution to journalArticle

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