Signaling through PI3Kgamma: a common platform for leukocyte, platelet and cardiovascular stress sensing

Thromb Haemost. 2006 Jan;95(1):29-35.


The concerted activation of leukocytes and vessels shapes multiple physiological and pathological responses. A large number of these processes shares a common signal transduction platform involving the activation of plasma membrane bound G protein-coupled receptors (GPCRs). This event is usually amplified by the production of different intra-cellular second messenger molecules. Among these mediators, the phosphorylated lipid phosphatidylinositol (3,4,5)-trisphosphate (PIP3) produced by phosphoinositide 3-kinase gamma (PI3Kgamma) has recently emerged as a crucial signal in both vascular and white blood cells. The generation of mice lacking PI3Kgamma showed that the GPCR/PI3Kgamma/PIP3 signaling pathway controls diverse immune modulatory and vascular functions like respiratory burst, cell recruitment, mast cell reactivity, platelet aggregation, endothelial activation as well as smooth muscle contractility. The relative specificity of these events suggests that blocking PI3Kgamma function might turn out beneficial for diseases like inflammation, allergy, thrombosis, and major cardiovascular disorders like hypertension, thus offering a wide range of therapeutic opportunities.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / enzymology*
  • Chemotaxis, Leukocyte / drug effects*
  • Class Ib Phosphatidylinositol 3-Kinase
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Inflammation / enzymology
  • Inflammation / prevention & control
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Leukocytes / drug effects
  • Leukocytes / enzymology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet Aggregation
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction*


  • Anti-Inflammatory Agents
  • Enzyme Inhibitors
  • Isoenzymes
  • Phosphoinositide-3 Kinase Inhibitors
  • Receptors, G-Protein-Coupled
  • Class Ib Phosphatidylinositol 3-Kinase
  • PIK3CG protein, human
  • Pik3cg protein, mouse