PI3K/Akt in platelet integrin signaling and implications in thrombosis
PI3K/Akt in platelet integrin signaling and implications in thrombosis
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DOI：
10.1016/j.jbior.2015.06.001
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Torti, Mauro
中科院分区：
文献类型：
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作者：
Guidetti, Gianni F.;Canobbio, Ilaria;Torti, Mauro
血小板是无核循环细胞，其在止血中起关键作用，并且还涉及动脉血栓形成，动脉血栓形成是全球死亡的主要原因。血小板的生物学功能强烈依赖于它们对多种细胞外激动剂的反应性，所述细胞外激动剂调节它们在血管损伤部位与细胞外基质的粘附以及它们形成快速生长的细胞聚集体的能力。在细胞表面表达的膜受体中，整合素对血小板活化、粘附和聚集都至关重要。整合素对特异性配体的亲和力由在刺激的血小板中活化的细胞内信号传导途径调节，并且一旦接合，整合素本身在细胞内产生和传播信号以加强和巩固血小板应答和血栓形成。磷脂酰肌醇3-激酶（PI 3 Ks）已成为血小板活化中的关键参与者，并且它们直接涉及整联蛋白功能的调节。本文综述了PI 3 Ks在血小板整合素信号转导中的作用，重点介绍了I类PI 3 Ks及其下游效应子Akt在整合素由内向外和由外向内信号转导中的作用。PI 3 K/Akt通路的贡献，刺激整合素的参与和血小板活化血栓形成和稳定，也将讨论，以突出的可能性，以针对这些酶在有效的抗血栓治疗策略。(C)2015爱思唯尔有限公司版权所有。
Blood platelets are anucleated circulating cells that play a critical role in hemostasis and are also implicated in arterial thrombosis, a major cause of death worldwide. The biological function of platelets strongly relies in their reactiveness to a variety of extracellular agonists that regulate their adhesion to extracellular matrix at the site of vascular injury and their ability to form rapidly growing cell aggregates. Among the membrane receptors expressed on the cell surface, integrins are crucial for both platelet activation, adhesion and aggregation. Integrin affinity for specific ligands is regulated by intracellular signaling pathways activated in stimulated platelets, and, once engaged, integrins themselves generate and propagate signals inside the cells to reinforce and consolidate platelet response and thrombus formation. Phosphatidylinositol 3-Kinases (PI3Ks) have emerged as crucial players in platelet activation, and they are directly implicated in the regulation of integrin function. This review will discuss the contribution of PI3Ks in platelet integrin signaling, focusing on the role of specific members of class I PI3Ks and their downstream effector Akt on both integrin inside-out and outside-in signaling. The contribution of the PI3K/Akt pathways stimulated by integrin engagement and platelet activation in thrombus formation and stabilization will also be discussed in order to highlight the possibility to target these enzymes in effective anti-thrombotic therapeutic strategies. (C) 2015 Elsevier Ltd. All rights reserved.