Class-IA phosphoinositide 3-kinase p110β triggers GPCR-induced superoxide production in p110γ-deficient murine neutrophils

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. © the japanese pharmacological society.