PI3Kγ controls oxidative burst in neutrophils via interaction with PKCα and p47phox

Katja Lehmann , Jörg P Müller (1) , Bernhard Schlott , Philipp Skroblin , Dagmar Barz , Johannes Norgauer , Reinhard Wetzker

1 Institute for Molecular Cell Biology

Neutrophils release reactive oxygen species (ROS) as part of the innate inflammatory immune response. Phosphoinositide 3-kinase γ (PI3Kγ), which is induced by the bacterial peptide N-formyl-Met-Leu-Phe (fMLP), has been identified as an essential intracellular mediator of ROS production. However, the complex signalling reactions that link PI3Kγ with ROS synthesis by NADH oxidase have not yet been described in detail. We found that activation of neutrophils by fMLP triggers the association of PI3Kγ with protein kinase C α (PKCα). Specific inhibition of PI3Kγ suppresses fMLP-mediated activation of PKCα activity and ROS production, suggesting that the protein kinase activity of PI3Kγ is involved. Our data suggest that the direct interaction of PI3K γ with PKCα forms a discrete regulatory module of fMLP-dependent ROS production in neutrophils.

Mots clés: Life Sciences

Katja Lehmann, Jörg P Müller, Bernhard Schlott, Philipp Skroblin, Dagmar Barz, et al.. PI3Kγ controls oxidative burst in neutrophils via interaction with PKCα and p47phox. Biochemical Journal, 2009, 419 (3), pp.603-610. ⟨10.1042/BJ20081268⟩. ⟨hal-00479057⟩