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Class I PI 3-kinases signaling in platelet activation and thrombosis: PDK1/Akt/GSK3 axis and impact of PTEN and SHIP1.

Abstract : Class I phosphoinositide 3-kinases (PI3K) have been extensively studied in different models these last years and several isoforms are now promising drug targets to treat cancer and immune diseases. Blood platelets are non-nucleated cells critical for hemostasis and strongly involved in arterial thrombosis, a leading cause of death worldwide. Besides their role in hemostasis and thrombosis, platelets provide an interesting model to characterize the implication of the different isoforms of PI3K in signaling. They are specialized for regulated adhesion, particularly under high shear stress conditions found in arteries and use highly regulated signaling mechanisms to form and stabilize a thrombus. In this review we will highlight the role of class I PI3K in these processes and the pertinence of targeting them in the context of antithrombotic strategies but also the potential consequences on the bleeding risk of inhibiting the PI3K signaling in cancer therapy. The implication of upstream regulators of the most important isoforms of PI3K in platelets and their downstream effectors such as protein kinase B (PKB or Akt) and its target glycogen synthase kinase 3 (GSK3) will be discussed as well as the impact of PTEN and SHIP phosphatases as modulators of this pathway.
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https://www.hal.inserm.fr/inserm-01012057
Contributor : Marie Francoise Simon <>
Submitted on : Wednesday, June 25, 2014 - 1:14:50 PM
Last modification on : Friday, January 10, 2020 - 9:09:54 PM

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Pierre-Alexandre Laurent, Sonia Severin, Marie-Pierre Gratacap, Bernard Payrastre. Class I PI 3-kinases signaling in platelet activation and thrombosis: PDK1/Akt/GSK3 axis and impact of PTEN and SHIP1.. Adv Biol Regul, 2014, 54, pp.162-74. ⟨10.1016/j.jbior.2013.09.006⟩. ⟨inserm-01012057⟩

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