Distinction between glycoprotein IIIa and the 100-kDa membrane protein (aggregin) mediating ADP-induced platelet activation.
Distinction between glycoprotein IIIa and the 100-kDa membrane protein (aggregin) mediating ADP-induced platelet activation.
复制标题
糖蛋白 IIIa 和介导 ADP 诱导血小板活化的 100 kDa 膜蛋白（聚集蛋白）之间的区别。
DOI：
10.1016/0003-9861(88)90192-0
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发表时间：
1988
影响因子：
3.9
通讯作者：
Niewiarowski,S
中科院分区：
文献类型：
--
作者：
Colman,RW;Figures,WR;Wu,QX;Chung,SY;Morinelli,TA;Tuszynski,GP;Colman,RF;Niewiarowski,S
我们实验室的前期研究表明，5′-对氟磺酰基苯甲酰基腺苷（FSBA）可抑制ADP诱导的血小板变形、聚集和纤维蛋白原位点的暴露，同时与完整血小板上的100 kDa血小板膜蛋白（aggregin）共价结合。胰凝乳蛋白酶将聚集蛋白酶解为70 kDa的片段，消除抑制作用，并将血小板糖蛋白IIIa（GPIIIa）（100 kDa）切割为含有P1 A1表位的70 kDa片段。我们质疑这些血小板膜蛋白是否是不同的。5′-p-[3 H]磺酰苯甲酰基腺苷（SBA）标记的聚集蛋白和125 I-GPIIIa均被血小板膜100 kDa部分的多克隆抗体沉淀，但聚集蛋白不能被沉淀GPIIIa的P1 A1的单特异性抗体沉淀。此外，与蛋白A-Sepharose偶联的免疫纯化的GPIIIa的单特异性多克隆抗体吸附GPIIIa，但不吸附聚集素。类似地，凝集素和GPIIIa均被血小板膜分离的70-kDa组分的多克隆抗体沉淀，但只有GPIIIa被GPIIIa的单克隆抗体沉淀（SSA 6）。两名Glanzman血栓无力症患者，其血小板膜含有<5%的GPIIIa（通过单克隆抗体结合（A2 A6）测定），掺入[3 H]SBA的程度与正常个体相同。此外，FSBA抑制ADP诱导的形状变化，具有类似的浓度依赖性的血小板和正常血小板。最后，十二烷基硫酸钠-聚丙烯酰胺凝胶电泳上的GPIIIa的流动性降低后，减少与二硫苏糖醇，而[3 H] SBA标记的MP 100没有改变。我们得出结论，GPIIIa和聚集素是不同的血小板膜蛋白。
Previous studies from our laboratories showed that 5′-p-fluorosulfonylbenzoyl adenosine (FSBA) inhibits ADP-induced platelet shape change, aggregation, and exposure of fibrinogen sites while covalently binding to 100-kDa platelet membrane protein (aggregin) on the intact platelet. Chymotrypsin digests aggregin to a fragment of 70 kDa, abolishing the inhibition, and also cleaves platelet glycoprotein IIIa (GPIIIa) (100 kDa) to a 70-kDa fragment containing the P1A1epitope. We questioned whether these platelet membrane proteins were distinct. Both 5′-p-[3H]sulfonylbenzoyl adenosine (SBA)-labeled aggregin and125I-GPIIIa were precipitated by polyclonal antibodies to a 100-kDa fraction of platelet membranes, but aggregin was not precipitated by a monospecific antibody to P1A1which precipitates GPIIIa. Further a monospecific polyclonal antibody to immunopurified GPIIIa coupled to protein A-Sepharose adsorbed GPIIIa but not aggregin. Similarly, both aggregin and GPIIIa were precipitated by a polyclonal antibody to an isolated 70-kDa component of platelet membrane but only GPIIIa was precipitated by the monoclonal antibody to GPIIIa, (SSA6). Two patients with Glanzman's thrombasthenia whose platelet membranes contained <5% GPIIIa as assayed by monoclonal antibody binding (A2A6), incorporated [3H]SBA to the same extent as normal individuals. Furthermore, FSBA inhibited ADP-induced shape change with a similar concentration dependence for both thrombasthenic and normal platelets. Finally, mobility of GPIIIa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was decreased following reduction with dithiothreitol whereas that of [3H]SBA-labeled MP 100 was not altered. We conclude that GPIIIa and aggregin are distinct platelet membrane proteins.