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Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics
Biochemical Journal ( IF 4.4 ) Pub Date : 2020-11-27 , DOI: 10.1042/bcj20190402
Agnès Ribes 1, 2 , Antoine Oprescu 1 , Julien Viaud 1 , Karim Hnia 1 , Gaëtan Chicanne 1 , Jean-Marie Xuereb 1 , Sonia Severin 1 , Marie-Pierre Gratacap 1 , Bernard Payrastre 1, 2
Affiliation  

Our knowledge on the expression, regulation and roles of the different phosphoinositide 3-kinases (PI3Ks) in platelet signaling and functions has greatly expanded these last twenty years. Much progress has been made in understanding the roles and regulations of class I PI3Ks which produce the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3). Selective pharmacological inhibitors and genetic approaches have allowed researchers to generate an impressive amount of data on the role of class I PI3Kα, β, δ and γ in platelet activation and in thrombosis. Furthermore, platelets do also express two class II PI3Ks (PI3KC2α and PI3KC2β), thought to generate PtdIns(3,4)P2 and PtdIns3P, and the sole class III PI3K (Vps34), known to synthesize PtdIns3P. Recent studies have started to reveal the importance of PI3KC2α and Vps34 in megakaryocytes and platelets, opening new perspective in our comprehension of platelet biology and thrombosis. In this review, we will summarize previous and recent advances on platelet PI3Ks isoforms. The implication of these kinases and their lipid products in fundamental platelet biological processes and thrombosis will be discussed. Finally, the relevance of developing potential antithrombotic strategies by targeting PI3Ks will be examined.

中文翻译:

血小板中的磷酸肌醇3激酶,血栓形成和治疗方法

在过去的20年中,我们对不同磷酸肌醇3激酶(PI3K)在血小板信号传导和功能中的表达,调控和作用的了解已大大扩展。在理解产生脂质第二信使磷脂酰肌醇3,4,5三磷酸(PtdIns(3,4,5)P3)的I类PI3K的作用和调控方面已取得了很大进展。选择性药理抑制剂和遗传方法已使研究人员获得了大量有关I类PI3Kα,β,δ和γ在血小板活化和血栓形成中的作用的数据。此外,血小板也确实表达了两个II类PI3K(PI3KC2α和PI3KC2β),它们被认为可以生成PtdIns(3,4)P2和PtdIns3P,还有唯一的III类PI3K(Vps34),已知可以合成PtdIns3P。最近的研究已经开始揭示PI3KC2α和Vps34在巨核细胞和血小板中的重要性,为我们理解血小板生物学和血栓形成开辟了新的前景。在这篇综述中,我们将总结血小板PI3K同工型的先前和最新进展。将讨论这些激酶及其脂质产物对血小板的基本生物学过程和血栓形成的影响。最后,将研究通过靶向PI3Ks开发潜在的抗血栓形成策略的相关性。将讨论这些激酶及其脂质产物对血小板的基本生物学过程和血栓形成的影响。最后,将研究通过靶向PI3Ks开发潜在的抗血栓形成策略的相关性。将讨论这些激酶及其脂质产物对血小板的基本生物学过程和血栓形成的影响。最后,将研究通过靶向PI3Ks开发潜在的抗血栓形成策略的相关性。
更新日期:2020-11-27
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