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Originally published In Press as doi:10.1074/jbc.M801876200 on April 22, 2008
J. Biol. Chem., Vol. 283, Issue 26, 17805-17814, June 27, 2008
Basigin-2 Is a Cell Surface Receptor for Soluble Basigin Ligand*
Robert J. Belton, Jr.1,
Li Chen,
Fernando S. Mesquita, and
Romana A. Nowak
From the
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801
The metastatic spread of a tumor is dependent upon the ability of the tumor to stimulate surrounding stromal cells to express enzymes required for tissue remodeling. The immunoglobulin superfamily protein basigin (EMMPRIN/CD147) is a cell surface glycoprotein expressed by tumor cells that stimulates matrix metalloproteinase and vascular endothelial growth factor expression in stromal cells. The ability of basigin to stimulate expression of molecules involved in tissue remodeling and angiogenesis makes basigin a potential target for the development of strategies to block metastasis. However, the identity of the cell surface receptor for basigin remains controversial. The goal of this study was to determine the identity of the receptor for basigin. Using a novel recombinant basigin protein (rBSG) corresponding to the extracellular domain of basigin, it was demonstrated that the native, nonglycosylated rBSG protein forms dimers in solution. Furthermore, rBSG binds to the surface of uterine fibroblasts, activates the ERK1/2 signaling pathway, and induces expression of matrix metalloproteinases 1, 2, and 3. Proteins that interact with rBSG were isolated using a biotin label transfer technique and sequenced by matrix-assisted laser desorption ionization tandem mass spectrophotometry. The results demonstrate that rBSG interacts with basigin expressed on the surface of fibroblasts and is subsequently internalized. During internalization, rBSG associates with a novel form of human basigin (basigin-3). It was concluded that cell surface basigin functions as a membrane receptor for soluble basigin and this homophilic interaction is not dependent upon glycosylation of the basigin ligand.
Received for publication, March 7, 2008
* This work was supported, in whole or in part, by National Institutes of Health Grant U54 HD40093 (to R. A. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.
1 Supported in part by a fellowship from the Lalor Foundation. To whom correspondence should be addressed: Dept. of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Dr., Urbana, IL 61801. Tel.: 217-265-0435; Fax: 217-333-8286; E-mail: rbelton{at}uiuc.edu.

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[Abstract]
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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
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