Intracellular signaling in platelets
Intracellular signaling in platelets
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DOI：
10.1097/01.moh.0000176681.18710.e3
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发表时间：
2005-09-01
影响因子：
3.2
通讯作者：
Abrams, CS
中科院分区：
文献类型：
--
作者：
Abrams, CS
综述目的在过去的几年里，很大一部分血小板研究集中在有助于稳定的血小板黏附和聚集的细胞内信号事件。最近对基因敲除小鼠的研究表明，几个以前未被认识的信号分子包括磷脂酰肌醇3-激酶、交换因子CalDAG-GEFI和小GTP酶Rap1b发挥了关键作用。这些蛋白质可能起到重塑血小板细胞骨架的作用，从而调节黏附和聚集。丰富的细胞骨架蛋白Talin似乎是血小板整合素αIIbβ3的关键调节因子。最近的证据表明，talin与β(3)胞浆尾部结合促进了整合素寡聚化，从而增加了与纤维蛋白原的结合亲和力。总结：血小板信号通路的识别不仅对诊断具有临床意义，而且可能更重要的是对合理的药物设计具有意义。阿司匹林、潘生丁(潘生丁)和硫代吡啶(噻氯匹定和氯吡格雷)都是专门针对离散的血小板信号通路的药物。这些药物已被证明对心血管疾病的治疗是有益的。以新发现的信号通路为靶点的新型药物有望获得更高的特异性和有效性。
Purpose of review Over the past few years, a large portion of platelet research has focused on intracellular signalling events that contribute to stable platelet adhesion and aggregation.Recent findings Studies of knockout mice have suggested critical roles fro several previously unappreciated signaling molecules including phosphatidylinositol 3-kinase, the exchange factor CalDAG-GEFI, and the small GTPase Rap1b. These proteins may function to remodel the platelet cytoskeleton and therby regulate both adhesion and aggregation. The abundant cytoskeletal protein talin appears to be a key regulator of the platelet integrin alpha IIb beta 3. Recent evidence suggests that talin binding to the cytoplasmic tail of beta(3) promotes integrin oligomerization, thereby increasing the binding avidity the alpha IIb beta 3 complex for fibrinogen.Summary The identification of platelet signalling pathways not only has clinical implications for diagnosis, but perhaps more importantly for rationale drug design. Aspirin, dipryidamole (Persantine), and thienopyridines (ticlopidine and clopidogrl) are all examples of agents that specifically target discrete platelet signaling pathways. These drugs have been proven to be beneficial in the treatment of cardiovascular disease. Novel agents that target newly identified signaling pathways hold promise of greater specificity and efficacy.