Function of PI3Kγ in thymocyte development, T cell activation, and neutrophil migration

Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice Lacking the p110 catalytic subunit of PI3K gamma were generated. We show that PI3K gamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3K gamma-deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric CTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3K gamma Links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3K gamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.