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.
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November 2020
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In this issue Kalogeropulou and colleagues (pp. 4397–4423) demonstrate that endogenous Rab29 does not impact basal or stimulated LRRK2 pathway activity. The cover image shows stained transgenic Rab29-overexpressing mouse cells. Image provided by Dario Alessi.
Review Article|
November 26 2020
Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics
Agnès Ribes;
Agnès Ribes
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
2Laboratoire D'Hématologie, CHU de Toulouse, 31059 Toulouse Cedex 03, France
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Antoine Oprescu;
Antoine Oprescu
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Julien Viaud;
Julien Viaud
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Karim Hnia;
Karim Hnia
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Gaëtan Chicanne;
Gaëtan Chicanne
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Jean-Marie Xuereb;
Jean-Marie Xuereb
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Sonia Severin;
Sonia Severin
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Marie-Pierre Gratacap;
Marie-Pierre Gratacap
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
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Bernard Payrastre
1Inserm U1048 and Université Toulouse III Paul Sabatier, I2MC, 31024 Toulouse Cedex 03, France
2Laboratoire D'Hématologie, CHU de Toulouse, 31059 Toulouse Cedex 03, France
Correspondence: Bernard Payrastre (bernard.payrastre@inserm.fr)
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Publisher: Portland Press Ltd
Received:
July 21 2020
Revision Received:
October 20 2020
Accepted:
November 04 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (22): 4327–4342.
Article history
Received:
July 21 2020
Revision Received:
October 20 2020
Accepted:
November 04 2020
Citation
Agnès Ribes, Antoine Oprescu, Julien Viaud, Karim Hnia, Gaëtan Chicanne, Jean-Marie Xuereb, Sonia Severin, Marie-Pierre Gratacap, Bernard Payrastre; Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics. Biochem J 27 November 2020; 477 (22): 4327–4342. doi: https://doi.org/10.1042/BCJ20190402
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