title: The role of class I, II and III PI 3-kinases in platelet production and activation and their implication in thrombosis.
abstract: Blood platelets play a pivotal role in haemostasis and are strongly involved in arterial thrombosis, a leading cause of death worldwide. Besides their critical role in pathophysiology, platelets represent a valuable model to investigate, both in vitro and in vivo, the biological roles of different branches of the phosphoinositide metabolism, which is highly active in platelets. While the phospholipase C (PLC) pathway has a crucial role in platelet activation, it is now well established that at least one class I phosphoinositide 3-kinase (PI3K) is also mandatory for proper platelet functions. Except class II PI3Kγ, all other isoforms of PI3Ks (class I α, β, γ, δ; class II α, β and class III) are expressed in platelets. Class I PI3Ks have been extensively studied in different models over the past few decades and several isoforms are promising drug targets to treat cancer and immune diseases. In platelet activation, it has been shown that while class I PI3Kδ plays a minor role, class I PI3Kβ has an important function particularly in thrombus growth and stability under high shear stress conditions found in stenotic arteries. This class I PI3K is a potentially interesting target for antithrombotic strategies. The role of class I PI3Kα remains ill defined in platelets. Herein, we will discuss our recent data showing the potential impact of inhibitors of this kinase on thrombus formation. The role of class II PI3Kα and β as well as class III PI3K (Vps34) in platelet production and function is just emerging. Based on our data and those very recently published in the literature, we will discuss the impact of these three PI3K isoforms in platelet production and functions and in thrombosis.
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Colin
authors.initials: C
authors.lastname: Valet
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Severin
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Chicanne
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Pierre Alexandre
authors.initials: PA
authors.lastname: Laurent
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gaits-Iacovoni
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gratacap
authors.affiliation: Inserm U1048, I2MC and Université Paul Sabatier, 31432, Toulouse Cedex 04, France; CHU de Toulouse, Laboratoire d'Hématologie, 31059, Toulouse Cedex 03, France. Electronic address: bernard.payrastre@inserm.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005786:Gene Expression Regulation; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D034061:Thrombopoiesis / Q000235:genetics; D013927:Thrombosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D010738:Type C Phospholipases
keywords: PI 3-kinase isoforms; Platelets; Signal transduction; Thrombosis