Protein disulphide isomerase in platelet function
Protein disulphide isomerase in platelet function
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DOI：
10.1111/j.1365-2141.2007.06898.x
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发表时间：
2008-01-01
影响因子：
6.5
通讯作者：
Essex, David W.
中科院分区：
文献类型：
--
作者：
Manickam, Nagaraj;Sun, Xiuhua;Essex, David W.
血小板蛋白二硫化物异构酶 (PDI) 在血小板聚集中发挥作用，可能针对含硫醇的血小板表面蛋白。含硫醇的 P2Y(12) ADP 受体参与大多数激动剂诱导的聚集，并且可能是 PDI 的靶点。通过排除 P2Y(12) 途径并使用抗 PDI 抗体 RL90，本研究表明 PDI 靶向聚集中的非 P2Y(12) 硫醇蛋白。抗 PDI 抑制 Mn2+ 对含硫醇的纤维蛋白原受体 α IIb beta 3 的信号独立激活，表明 PDI 直接与 α IIb beta 3 相互作用。随着血小板活化，含硫醇形式的 PDI 在血小板表面增加，表明活性 PDI 很容易可用于 α IIb beta 3 的氧化还原调节。最后，使用纯化的蛋白质，PDI 比 α IIb 具有更大的异构化二硫键的能力beta 3 整合素，也具有类似 PDI 的活性。总之，血小板中存在一种增加表面 PDI 功能形式的机制，并且该 PDI 具有非 P2Y(12) 靶标，可能是 α IIb beta 3。
Platelet protein disulphide isomerase (PDI) has a role in platelet aggregation, probably targeting a thiol-containing platelet surface protein. The thiol-containing P2Y(12) ADP receptor is involved in aggregation induced by most agonists and may be the target of PDI. By excluding the P2Y(12) pathway and using the anti-PDI antibody RL90 this study showed that PDI targets a non-P2Y(12) thiol-protein in aggregation. Anti-PDI inhibited signalling-independent activation of the thiol-containing fibrinogen receptor alpha IIb beta 3 by Mn2+, suggesting that PDI directly interacts with alpha IIb beta 3. The thiol-containing form of PDI increased on the platelet surface with platelet activation, suggesting that active PDI readily becomes available for redox regulation of alpha IIb beta 3. Finally, using purified proteins PDI had greater ability to isomerize disulphide bonds than the alpha IIb beta 3 integrin, which also has PDI-like activity. In summary, a mechanism exists in platelets to increase the functional form of surface PDI and this PDI has a non-P2Y(12) target that may be alpha IIb beta 3.