Targeting phosphoinositide 3-kinase gamma to fight inflammation and more.
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 (PI3Kgamma) is activated by G protein coupled receptors (GPCRs), like chemokine receptors. PI3Kgamma 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 PI3Kgamma in leukocytes and in endothelial cells. Results, derived from studies based on both pharmacological and genetic approaches, confirm PI3Kgamma as an attractive target for drug discovery. PI3Kgamma 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.
Barberis
Laura
L
Molecular Biotechnology Center and Department of Genetics, Biology and Biochemistry, University of Torino, Via Nizza 52, 10126 Turin, Italy.
Hirsch
Emilio
E
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D058544:Class Ib Phosphatidylinositol 3-Kinase; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C546760:PIK3CG protein, human