Signaling through PI3Kγ:: a common platform for leukocyte, platelet and cardiovascular stress sensing

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 (PI3K gamma) has recently emerged as a crucial signal in both vascular and white blood cells. The generation of mice lacking PI3K gamma showed that the GPCR/PI3K gamma/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 PI3K gamma 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.