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Emilio Hirsch, Giuseppe Lembo, Giuseppe Montrucchio, Christian Rommel, Carlotta Costa, Laura Barberis

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

Thrombosis and Haemostasis, Schattauer

Print ISSN: 0340-6245
Volume: 95, 01/2006
Pages: 29 - 35

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