Stimulation of Human Neutrophils by Chemotactic Factors Is Associated with the Activation of Phosphatidylinositol 3-Kinase γ*

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dc.contributor.authorNaccache, P.
dc.contributor.authorLevasseur, S.
dc.contributor.authorLachance, G.
dc.contributor.authorChakravarti, S.
dc.contributor.authorBourgoin, S.
dc.contributor.authorMcColl, S.
dc.date.issued2000
dc.description.abstractThe 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.
dc.description.statementofresponsibilityPaul H. Naccache, Sylvain Levasseur, Genevie, ve Lachance, Sumone Chakravarti, Sylvain G. Bourgoini, and Shaun R. McColl
dc.identifier.citationJournal of Biological Chemistry, 2000; 275(31):23636-23641
dc.identifier.doi10.1074/jbc.M001780200
dc.identifier.issn0021-9258
dc.identifier.issn0021-9258
dc.identifier.orcidMcColl, S. [0000-0003-0949-4660]
dc.identifier.urihttp://hdl.handle.net/2440/28030
dc.language.isoen
dc.publisherElsevier
dc.rights© 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.
dc.source.urihttps://doi.org/10.1074/jbc.m001780200
dc.subjecthuman; polymorphonuclear neutrophil leukocytes (neutrophils); highly phosphorylated phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3); G protein-dependent phosphatidylinositol 3-kinase (PI3K); p110γ; investigation
dc.titleStimulation of Human Neutrophils by Chemotactic Factors Is Associated with the Activation of Phosphatidylinositol 3-Kinase γ*
dc.typeJournal article
pubs.publication-statusPublished

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