Basigin-2 is a cell surface receptor for soluble basigin ligand
Basigin-2 is a cell surface receptor for soluble basigin ligand
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DOI：
10.1074/jbc.m801876200
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发表时间：
2008-06-27
影响因子：
4.8
通讯作者：
Nowak, Romana A.
中科院分区：
文献类型：
--
作者：
Belton, Robert J., Jr.;Chen, Li;Nowak, Romana A.
肿瘤的转移性扩散依赖于肿瘤刺激周围基质细胞表达组织重塑所需的酶的能力。免疫球蛋白超家族蛋白basigin（EMMPRIN/CD 147）是由肿瘤细胞表达的细胞表面糖蛋白，其刺激基质细胞中的基质金属蛋白酶和血管内皮生长因子表达。basigin刺激参与组织重塑和血管生成的分子表达的能力使得basigin成为开发阻断转移策略的潜在靶标。然而，basigin的细胞表面受体的身份仍然存在争议。本研究的目的是确定basigin受体的身份。使用一种新的重组basigin蛋白（rBSG）对应于basigin的胞外结构域，它被证明，天然的，非糖基化的rBSG蛋白在溶液中形成二聚体。此外，rBSG结合到子宫成纤维细胞的表面，激活ERK 1/2信号通路，并诱导基质金属蛋白酶1、2和3的表达。使用生物素标记转移技术分离与rBSG相互作用的蛋白质，并通过基质辅助激光解吸电离串联质谱法进行测序。结果表明，rBSG与成纤维细胞表面表达的basigin相互作用，随后被内化。在内化过程中，rBSG与一种新形式的人basigin（basigin-3）相关联。得出结论，细胞表面basigin作为可溶性basigin的膜受体发挥作用，并且这种亲嗜性相互作用不依赖于basigin配体的糖基化。
Themetastatic 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.