Secondary dimerization between members of the epidermal growth factor receptor family

Daniel C. Gamett, Gray Pearson, Richard A. Cerione, Ilan Friedberg

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Growth factor receptors of the epidermal growth factor (EGF) receptor family play pivotal roles in the regulation of cell proliferation and differentiation and are involved in the development of human cancers.It has been well documented that these receptors undergo growth factor-stimulated homo- and heterodimerization as a first step in the initiation of signaling cascades. Here we provide evidence for a new mechanism for growth factor- stimulated receptor dimer formation, designated secondary dimerization. The growth factor-induced dimerization and ensuing receptor trans- autophosphorylation results in the dissociation of the original (primary) receptor dimer. Each phosphorylated receptor monomer then interacts with a new (nonphosphorylated) receptor to form a secondary dimer. Treatment of cells with EGF yields Neu-ErbB3 secondary dimers, and heregulin treatment induces the formation of Neu-EGF receptor (secondary) dimers. The ability of EGF and heregulin to stimulate a cascade of dimerization events points to a novel mechanism by which multiple signaling activities and diverse biological responses are initiated by members of the EGF receptor family.

Original languageEnglish (US)
Pages (from-to)12052-12056
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number18
DOIs
StatePublished - May 2 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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