Journal
BIOCHEMICAL JOURNAL
Volume 419, Issue -, Pages 603-610Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20081268
Keywords
neutrophil; phosphoinositide 3-kinase gamma (PI3K gamma); protein kinase C alpha (PKC alpha); protein kinase; reactive oxygen species
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Funding
- Deutsche Forschungsgemeinschaft [SFB 604]
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Neutrophils release reactive oxygen species (ROS) as part of the innate inflammatory immune response. Phosphoinositide 3-kinase gamma (PI3K gamma), which is indUced by the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), has been identitied as an essential intracellular mediator of ROS production. However, the complex signalling reactions that link PI3K gamma with ROS synthesis by NADPH oxidase have not yet been described in detail. We found that activation of neutrophils by fMLP triggers the association of PI3K gamma with protein kinase C alpha (PKC alpha). Specific inhibition of PI3K gamma suppresses fMLP-mediated activation of PKC alpha activity and ROS production, suggesting that the protein kinase activity of PI3K gamma is involved. Our data suggest that the direct interaction of PI3K gamma with PKC alpha forms it discrete regulatory module of fMLP-dependent ROS production in neutrophils.
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