Naccache, P.Levasseur, S.Lachance, G.Chakravarti, S.Bourgoin, S.McColl, S.2007-05-112007-05-112000Journal of Biological Chemistry, 2000; 275(31):23636-236410021-92580021-9258http://hdl.handle.net/2440/28030The activation of human polymorphonuclear neutrophil leukocytes (neutrophils) is associated with an increased synthesis of the highly phosphorylated phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). The aims of the present investigation were to determine whether the newly described, G protein-dependent phosphatidylinositol 3-kinase (PI3K), p110γ, was involved in the responses to chemotactic factors interacting with G protein-coupled receptors. The presence of p110γ in neutrophils was first established both at the protein and the mRNA level. Stimulation of the cells with fMet-Leu-Phe or interleukin-8 increased the PI3K activity in p110γ, but not p85, immunoprecipitates. The time course of this effect (threshold within less than 5 s, maximal activation at 10–15 s) was consistent with that of the generation of PtdIns(3,4,5)P3. Wortmannin, a PI3K inhibitor, abrogated the effects of fMet-Leu-Phe, which were also significantly inhibited by pertussis toxin. Finally, fMet-Leu-Phe also induced a significant translocation of p110γ to a particulate fraction derived from these cells. These data indicate that p110γ represent the major PI3K activated by fMet-Leu-Phe and interleukin-8 at very early time points following the stimulation of human neutrophils.en© 2000 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. This is an Open Access article under the CC BY license.human; polymorphonuclear neutrophil leukocytes (neutrophils); highly phosphorylated phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3); G protein-dependent phosphatidylinositol 3-kinase (PI3K); p110γ; investigationJournal article000100211010.1074/jbc.M0017802000000885642000332-s2.0-003460456962827McColl, S. [0000-0003-0949-4660]