Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C.
Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C.
复制标题
神经胶质肿瘤细胞粘附是通过受体蛋白酪氨酸磷酸酶 β (RPTPβ) 的 FNIII 结构域与腱蛋白 C 的结合介导的。
作者：
K. Adamsky;J. Schilling;J. Garwood;A. Faissner;E. Peles
受体蛋白酪氨酸磷酸酶β (rptpβ)的胞外结构域由几个结构域组成，这些结构域介导其与存在于神经元或胶质细胞表面的不同配体的相互作用。在这里，我们证明了RPTPbeta的纤维连接蛋白III型结构域（FNIII）与胶质肿瘤来源的细胞系和原代星形胶质细胞结合。我们使用亲和纯化分离了几个特异性结合RPTPbeta的FNIII结构域的蛋白。其中，从U118MG胶质母细胞瘤细胞中纯化的240 kDa蛋白，根据几个色氨酸肽的氨基酸序列确定为腱蛋白C。发现RPTPbeta与腱素C的相互作用介导细胞粘附。表达RPTPbeta的SF763T星形细胞瘤细胞在tenascin C上的粘附和扩散被添加含有受体FNIII结构域的可溶性片段特异性地消除。RPTPbeta依赖的细胞粘附通过结合tenascin c的选择性剪接的FNIII重复序列A1,2,4 （tnfna1,2,4）介导。此外，表达RPTPbeta的COS细胞粘附tnfna1,2,4，而亲本细胞不粘附。这些结果表明，RPTPbeta的FNIII结构域与tenascin C结合，并表明存在于胶质肿瘤细胞上的RPTPbeta是细胞外基质的主要粘附受体系统。
The extracellular domain of receptor protein tyrosine phosphatase beta (RPTPbeta) is composed of several domains which mediate its interactions with distinct ligands present on the surface of either neurons or glial cells. Here, we demonstrate that the fibronectin type III domain (FNIII) of RPTPbeta binds to glial tumor-derived cell lines and primary astrocytes. We used affinity purification to isolate several proteins that specifically bind to the FNIII domain of RPTPbeta. One of these, a 240 kDa protein that was purified from U118MG glioblastoma cell, was identified as tenascin C based on the amino acid sequence of several tryptic peptides. The interaction of RPTPbeta with tenascin C was found to mediate cell adhesion. Adhesion and spreading of SF763T astrocytoma cells expressing RPTPbeta on tenascin C was specifically abolished by the addition of a soluble fragment containing the FNIII domain of the receptor. RPTPbeta-dependent cell adhesion was mediated by binding to the alternatively spliced FNIII repeats A1,2,4 (TnfnA1,2,4) of tenascin C. Furthermore, COS cells expressing RPTPbeta adhere to TnfnA1,2,4, while the parental cells did not. These results demonstrate that the FNIII domain of RPTPbeta binds to tenascin C and suggest that RPTPbeta present on glial tumor cells is a primary adhesion receptor system to the extracellular matrix.