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Targeting phosphoinositide 3-kinase γ to fight inflammation and more

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

From Molecules to Medicine: New Horizons in Vascular Biology and Thrombosis (Part I)

DOI: http://dx.doi.org/10.1160/TH07-10-0632
Issue: 2008: 99/2 (Feb) pp. 249-455
Pages: 279-285

Targeting phosphoinositide 3-kinase γ to fight inflammation and more

Laura Barberis, Emilio Hirsch

Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Torino; Italy

Keywords

inflammation, signal transduction, endothelial cells, leukocyte trafficking / recruitment

Summary

The family of class I phosphoinositide-3-kinase (PI3K) is composed of four lipid kinases involved at multiple levels in innate and adaptive immune responses. Class I PI3Ks are divided into two subclasses, IA and IB, sharing a similar catalytic core. Whereas class IA PI3Ks are primarily activated by receptor tyrosine kinases, the unique element of class IB PI3K (PI3Kγ) is activated by G protein coupled receptors (GPCRs), like chemokine receptors. PI3Kγ is mainly expressed in leukocytes where it plays a significant role in chemotaxis. Here, we report recent advances in the analysis of the role of PI3Kγ in leukocytes and in endothelial cells. Results, derived from studies based on both pharmacological and genetic approaches,confirm PI3Kγ as an attractive target for drug discovery. PI3Kγ specific inhibition has gained increasing attention for the treatment of allergic, autoimmune and inflammatory diseases. Development of inhibitors has already provided series of hits, whose efficacy is currently under scrutiny worldwide.

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