Scott J L, Dunn S M, Jin B, Hillam A J, Walton S, Berndt M C, Murray A W, Krissansen G W, Burns G F
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
J Biol Chem. 1989 Aug 15;264(23):13475-82.
When platelets bind certain specific ligands they are induced to secrete the contents of their cytoplasmic granules and to aggregate. Studies of the molecular events accompanying this vital physiological response have led to a greater understanding of cell activation in general since the pathways involved are common to a number of cell types. By contrast most of the information about the cell surface molecules that initiate signal transduction has emerged from work on T lymphocyte activation, a process essential to the initiation of the immune response. We have described an activation antigen on T lymphocytes that is involved in the differentiation of these cells. In the present report it is demonstrated that the antigen is expressed on the platelet membrane with about 1,200 copies/platelet. A monoclonal antibody detecting this antigen stimulates platelet secretion and aggregation with a half-maximal response at approximately 10(-8) M. Characterization of the antigen, termed PTA1, reveals a glycoprotein of Mr 67,000 showing extensive N-linked carbohydrate, much of which appears to be heavily sialated. The amino-terminal sequence of PTA1, EEVLWHTSVPFAEXMSLEXVYPSM, indicates that the protein has not previously been characterized. Preliminary investigation of the mechanism by which PTA1 mediates platelet activation suggests involvement of protein kinase C and the 47-kDa protein of platelets is rapidly phosphorylated upon antibody-mediated activation. During this process PTA1 is also phosphorylated, as it is following platelet activation by the other agonists, collagen, thrombin, and 12-O-tetradecanoylphorbol 13-acetate. These results provide the first example of a cell surface glycoprotein that is directly involved in both platelet and T lymphocyte activation.
当血小板结合某些特定配体时，它们会被诱导分泌其细胞质颗粒的内容物并发生聚集。对伴随这种重要生理反应的分子事件的研究，使人们对细胞活化有了更深入的总体认识，因为所涉及的途径在许多细胞类型中是共有的。相比之下，关于启动信号转导的细胞表面分子的大多数信息来自于对T淋巴细胞活化的研究，T淋巴细胞活化是免疫反应启动所必需的过程。我们已经描述了一种参与T淋巴细胞分化的活化抗原。在本报告中，证明该抗原以约1200个拷贝/血小板的数量表达于血小板膜上。一种检测该抗原的单克隆抗体可刺激血小板分泌和聚集，其半最大反应浓度约为10^(-8)M。对称为PTA1的抗原的特性分析显示，它是一种分子量为67000的糖蛋白，具有广泛的N-连接碳水化合物，其中大部分似乎含有大量唾液酸。PTA1的氨基末端序列为EEVLWHTSVPFAEXMSLEXVYPSM，表明该蛋白质以前未被鉴定过。对PTA1介导血小板活化机制的初步研究表明，蛋白激酶C参与其中，并且血小板的47kDa蛋白在抗体介导的活化后迅速被磷酸化。在此过程中，PTA1也被磷酸化，就像在血小板被其他激动剂（胶原、凝血酶和12-O-十四烷酰佛波醇13-乙酸酯）活化后一样。这些结果提供了第一个直接参与血小板和T淋巴细胞活化的细胞表面糖蛋白的例子。
