Secondary Dimerization between Members of the Epidermal Growth Factor Receptor Family*
- From the Department of Pharmacology, Veterinary Medical Center, Cornell University, Ithaca, New York 14853
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.
Footnotes
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↵* This work was supported by National Institutes of Health Grant GM40654, Department of Defense Grant DAMD17-94-J-4123, and by the Council for Tobacco Research Grant 4014 (to R. A. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Present address: Dept. of Surgery, SUNY Health Science Center, 750 E. Adams Street, Syracuse, NY 13210.
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↵§ Visiting scientist of the Dept. of Cell Research and Immunology, Tel Aviv University, 69978 Tel Aviv, Israel. To whom correspondence should be addressed. Tel.: 607-253-3873; Fax: 607-253-3659; E-mail:if14{at}cornell.edu.
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↵1 The abbreviations used are: EGF, epidermal growth factor; EGFR, EGF receptor; HRG, heregulin.
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↵2 D. Gamett, unpublished data.
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↵3 P. Guy and K. Carraway, unpublished data.
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- Received February 13, 1997.
