title: Class-IA phosphoinositide 3-kinase p110β Triggers GPCR-induced superoxide production in p110γ-deficient murine neutrophils.
abstract: Studies with knockout mice have indicated that the only isoform of phosphoinositide 3-kinase (PI3K) functioning in the oxidative burst of mouse neutrophils in response to heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) agonists is a class-IB PI3K, p110γ. In the present study, we observed that the cells from p110γ(-/-) mice gain a response to N-formyl-Met-Leu-Phe (fMLP) after priming with cytochalasin E. Even the unprimed cells, which show no response to fMLP, produce a significant amount of superoxide, when an effective agonist of the mouse-type fMLP receptors, Trp-Lys-Tyr-Met-Val-D-Met, is used to stimulate the cells. These results suggested that the class-IA isoforms (p110α, p110β, and p110δ) of PI3K are sufficient to trigger and maintain superoxide production. Examination of the effects of isoform-specific inhibitors suggested that the p110β isoform is the primary PI3K triggering the response to GPCR agonists when p110γ is absent.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan. knigo@hiroshima-u.ac.jp
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nigorikawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hazeki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumazawa
authors.forename: Yuhta
authors.initials: Y
authors.lastname: Itoh
authors.forename: Megumi
authors.initials: M
authors.lastname: Hoshi
authors.forename: Osamu
authors.initials: O
authors.lastname: Hazeki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000502:physiology*; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000172:deficiency*; D007527:Isoenzymes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D058543:Class Ia Phosphatidylinositol 3-Kinase; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse