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

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

doi:10.1160/TH05-07-0476

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 29-35
DOI: 10.1160/TH05-07-0476

Theme Issue Article

Schattauer GmbH

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

Emilio Hirsch

¹Dipartimento di Genetica, Biologia e Biochimica. Università di Torino. Torino. Italy

,

Giuseppe Lembo

²Department of Neurocardiology. Neuromed Institute. Pozzilli (Isernia). Italy

,

Giuseppe Montrucchio

³Dipartimento di Fisiopatologia Clinica. Università di Torino. Torino. Italy

,

Christian Rommel

⁴Serono Pharmaceutical Research Institute. Serono International S.A. Geneva. Switzerland

,

Carlotta Costa

¹Dipartimento di Genetica, Biologia e Biochimica. Università di Torino. Torino. Italy

,

Laura Barberis

¹Dipartimento di Genetica, Biologia e Biochimica. Università di Torino. Torino. Italy

› Author Affiliations

Abstract

Summary

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 γ (PI3Kγ) has recently emerged as a crucial signal in both vascular and white blood cells. The generation of mice lacking PI3Kγ showed that the GPCR/PI3Kγ/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 PI3Kγ 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.

Keywords

Signal transduction - inflammation - G protein-coupled receptors - phosphatidylinositol 3-kinase

Full Text

References

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