Blood Journal
Leading the way in experimental and clinical research in hematology

Brief report
Deletion of the p110β isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo

  1. Valérie Martin1,
  2. Julie Guillermet-Guibert2,
  3. Gaétan Chicanne1,
  4. Cendrine Cabou3,
  5. Martine Jandrot-Perrus4,
  6. Monique Plantavid1,
  7. Bart Vanhaesebroeck2,
  8. Bernard Payrastre1,*, and
  9. Marie-Pierre Gratacap1,*
  1. 1Inserm, U563, Centre de Physiopathologie de Toulouse Purpan, Département d'Oncogenèse, Signalisation et Innovation thérapeutique, and Université Toulouse III Paul-Sabatier, Toulouse, France;
  2. 2Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, London, United Kingdom;
  3. 3Inserm, U858, Institute of Molecular Medicine Rangueil, and Faculté des Sciences Pharmaceutiques, Toulouse, France; and
  4. 4Inserm, U698, Hôpital Bichat, Paris, France


During platelet activation, phosphoinositide 3-kinases (PI3Ks) produce lipid second messengers participating in the regulation of functional responses. Here, we generated a megakaryocyte-restricted p110β null mouse model and demonstrated a critical role of PI3Kβ in platelet activation via an immunoreceptor tyrosine-based activation motif, the glyco-protein VI-Fc receptor γ-chain complex, and its contribution in response to G-protein–coupled receptors. Interestingly, the production of phosphatidylinositol 3,4,5-trisphosphate and the activation of protein kinase B/Akt were strongly inhibited in p110β null platelets stimulated either via immunoreceptor tyrosine-based activation motif or G-protein–coupled receptors. Functional studies showed an important delay in fibrin clot retraction and an almost complete inability of these platelets to adhere onto fibrinogen under flow condition, suggesting that PI3Kβ is also acting downstream of αIIbβ3. In vivo studies showed that these mice have a normal bleeding time and are not protected from acute pulmonary thromboembolism but are resistant to thrombosis after FeCl3 injury of the carotid, suggesting that PI3Kβ is a potential target for antithrombotic drugs.

  • Submitted April 24, 2009.
  • Accepted December 4, 2009.
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