Regulation and roles of PI3Kβ, a major actor in platelet signaling and functions

Adv Enzyme Regul. 2011;51(1):106-16. doi: 10.1016/j.advenzreg.2010.09.011. Epub 2010 Oct 28.


Phosphoinositide 3-kinases (PI3Ks) are important signaling enzymes involved in the regulation of a number of critical cell functions. Significant progress has been made during the last few years in defining the implication of individual PI3K isoforms. The role of the class IA PI3Kβ in different cell types has only been recently uncovered by the use of isoform-selective inhibitors and the development of mouse models harboring p110β catalytic subunit knock-out or germline knock-in of a kinase-dead allele of p110β. Although it is classically admitted that class IA PI3Ks are activated by receptor tyrosine kinases through recruitment of the regulatory subunits to specific tyrosine phosphorylated motifs via their SH2 domains, PI3Kβ is activated downstream of G protein-coupled receptors, and by co-operation between heterotrimeric G proteins and tyrosine kinases. PI3Kβ has been extensively studied in platelets where it appears to play an important role downstream of ITAM signaling, G protein-coupled receptors and aIIbβ3 integrin. Accordingly, mouse exhibiting p110β inactivation selectively in megakaryocyte/platelets are resistant to thromboembolism induced by carotid injury. The present review summarizes recent data concerning the mechanisms of PI3Kβ regulation and the roles of this PI3K isoform in blood platelet functions and other cell types.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / enzymology*
  • Blood Platelets / physiology*
  • Collagen / metabolism
  • Enzyme Activation
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Phosphatidylinositol 3-Kinases / chemistry
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositols / metabolism
  • Platelet Aggregation / physiology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology*
  • von Willebrand Factor / metabolism


  • Isoenzymes
  • Phosphatidylinositols
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, G-Protein-Coupled
  • von Willebrand Factor
  • Collagen
  • Phosphatidylinositol 3-Kinases