Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion
Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion
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DOI：
10.1055/s-0037-1613070
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发表时间：
2002-04-01
影响因子：
6.7
通讯作者：
Kornecki, E
中科院分区：
文献类型：
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作者：
Babinska, A;Kedees, MH;Kornecki, E
F11受体（F11R）最初是在人血小板表面被鉴定为一种刺激性单克隆抗体（M.Ab.F11）的靶点，该抗体可诱导分泌，随后使纤维蛋白原受体暴露并引起聚集。F11R基因的克隆显示，这种蛋白质是一种细胞黏附分子（CAM），属于免疫球蛋白超家族成员，是小鼠连接黏附分子（JAM）的直系同源物。本研究确定了两个结构域，M.Ab.F11通过这两个结构域触发血小板反应，最终导致聚集。M.Ab.F11介导的血小板黏附以及M.Ab.F11对胶原蛋白和ADP诱导的血小板聚集的增强作用都涉及相同的两个结构域。一种F11R重组蛋白（sF11R）完全抑制了M.Ab.F11诱导的血小板聚集、黏附和增强作用，这表明F11R胞外结构域的活性构象存在于可溶性分泌重组蛋白中。此外，一种包含F11R的N端氨基酸S - 1至C - 23序列的特异性肽段，以及一种在F11R的第一个免疫球蛋白样（Ig）折叠中具有K - 70至C - 82序列的肽段，都抑制了M.Ab.F11诱导的人血小板聚集、黏附和聚集增强作用。人血小板F11R胞外结构域的三维结构建模表明，这两个区域在这种细胞黏附分子的构象内形成一个活性位点。F11R的这些功能结构域（在N端和第一个Ig折叠中）的序列为治疗某些类型的血小板减少症和炎症性血栓形成的新药开发提供了基础。
The F11 receptor (F11R) was first identified on the surface of human platelets as a target for a stimulatory monoclonal antibody (M.Ab.F11) that induces secretion. followed by exposure of fibrinogen receptors and aggregation, Cloning of the gene of F I I R has revealed that this protein is It cell adhesion molecule (CAM). a member of the Ig superfamily and an ortholog of the murine protein called junctional adhesion molecule (JAM). The present study has identified two domains through which M.Ab.F11 triggers a platelet response culminating with aggregation tion. M.Ah.F I I -mediated platelet adhesion, and the potentiation of collagen and ADP-induced platelet aggregation by M.Ab.F11. were found to involve the same two domains. A F11R recombinant protein (sF11R) completely inhibited platelet aggregation. adhesion and potentiation induced by M.Ab.F11, indicative that the active conformation of the external domain of F11R is present in the soluble. secreted recombinant protein. Furthermore. a specific peptide containing the sequence of the N-terminal amino acids S-1 to C-23 of F11R. and a peptide with the sequence of K-70 to C-82 in the 1(st) immunoglobulin-like (Ig) fold of F11R, both inhibited M.Ab.F11-induced aggregation. adhesion and potentiation of the aggregation of human platelets. Modeling of the 3D structure of the extracellular domain of the human platelet F11R suggests that these two regions form an active site within the conformation of this CAM. The sequence of these functional domains of F11R (in the N-terminus and 1(st) Ig-fold) provide the basis for new drug development in the treatment of certain types of thrombocytopenia and inflammatory thrombosis.