T-CELL ACTIVATION MOLECULE 4-1BB BINDS TO EXTRACELLULAR-MATRIX PROTEINS
T-CELL ACTIVATION MOLECULE 4-1BB BINDS TO EXTRACELLULAR-MATRIX PROTEINS
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DOI：
10.1073/pnas.89.21.10360
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
ARUFFO, A
中科院分区：
文献类型：
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作者：
CHALUPNY, NJ;PEACH, R;ARUFFO, A
新近分离的4-1BB基因克隆编码一种由活化的T细胞表达的细胞表面蛋白。它的胞外区与神经生长因子受体超家族的成员同源，其胞内区含有与T细胞特异性酪氨酸激酶p56lck结合位点的序列，该结合位点存在于CD4和CD8α的胞浆区。目前，4-1BB的功能尚不清楚。我们制备了4-1BB-免疫球蛋白融合蛋白(4-1BB Rg)。这种蛋白被用于免疫组织化学研究，以确定表达4-1BB配体的组织。4-1BB Rg与几乎所有被研究的组织结合，表明细胞外成分可能作为其配体发挥作用。为了探讨4-1BB与COS细胞结合的可能性，在COS细胞中表达了4-1BB，发现4-1BB可与纤维连接蛋白、玻璃体连接蛋白、层粘连蛋白和VI型胶原结合，但不能与I型胶原结合。细胞外基质蛋白与4-1BB的结合不受Arg-Gly-Asp(RGD)或CS-1氨基酸序列的影响。用重叠的纤维连接蛋白的蛋白分解片段进行的实验表明，4-1BB与纤维连接蛋白的多个区域相互作用。细胞外基质蛋白与4-1BB的相互作用可被阴离子碳水化合物聚合物岩藻糖胶完全阻断，被阴离子碳水化合物聚合物硫酸葡聚糖和硫酸氨基葡聚糖肝素部分阻断，但不受脱硫肝素的影响。这些结果提示，碳水化合物可能在介导4-1BB-细胞外基质蛋白的黏附中起作用。
The recently isolated 4-1BB cDNA clone encodes a cell surface protein expressed by activated T cells. Its extracellular domain is homologous to members of the nerve growth factor receptor super family and its cytoplasmic domain contains a sequence homologous to the binding site for the T-cell-specific tyrosine kinase p56lck found in the cytoplasmic domains of CD4 and CD8alpha. At present the function of 4-1BB is not known. We prepared a 4-1BB-immunoglobulin fusion protein (4-1BB Rg). This protein was used in immunohistochemical studies to identify tissues that express the 4-1BB ligand. 4-1BB Rg bound to virtually all tissues examined, suggesting that extracellular components might function as its ligands. To explore this possibility, 4-1BB was expressed in COS cells and found to mediate the binding of fibronectin, vitronectin, laminin, and collagen VI but not of collagen I. The binding of extracellular matrix proteins to 4-1BB was not mediated by Arg-Gly-Asp (RGD) or CS-1 amino acid sequences. Experiments with overlapping proteolytic fragments of fibronectin showed that 4-1BB interacts with multiple regions of fibronectin. The interaction between extracellular matrix proteins and 4-1BB was completely blocked by the anionic carbohydrate polymer fucoidan and was partially blocked by the anionic carbohydrate polymer dextran sulfate and the glycosaminoglycan heparin sulfate but was unaffected by desulfated heparin. These results suggest that carbohydrates may play a role in mediating the 4-1BB-extracellular matrix protein adhesion.