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-formylmethionyl-leucyl-phenylalanine (fMLP), has been identified as an essential intracellular mediator of ROS production. However, the complex signalling reactions that link PI3Kγ 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 PI3Kγ with protein kinase Cα (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 PI3Kγ with PKCα forms a discrete regulatory module of fMLP-dependent ROS production in neutrophils.
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May 2009
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Research Article|
April 14 2009
PI3Kγ controls oxidative bursts in neutrophils via interactions with PKCα and p47phox
Katja Lehmann;
Katja Lehmann
1
*Department of Dermatology, Friedrich Schiller University, Jena, Germany
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Jörg P. Müller;
†Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany
2To whom correspondence should be addressed (email joerg.mueller2@med.uni-jena.de).
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Bernhard Schlott;
Bernhard Schlott
‡Leibniz Institute for Age Research, Fritz-Lipmann-Institut e.V. (FLI), Jena, Germany
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Philipp Skroblin;
Philipp Skroblin
3
†Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany
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Dagmar Barz;
Dagmar Barz
¶Institute of Transfusion Medicine, Friedrich Schiller University, Jena, Germany
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Johannes Norgauer;
Johannes Norgauer
*Department of Dermatology, Friedrich Schiller University, Jena, Germany
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Reinhard Wetzker
Reinhard Wetzker
†Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany
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Publisher: Portland Press Ltd
Received:
June 23 2008
Revision Received:
October 31 2008
Accepted:
November 05 2008
Accepted Manuscript online:
November 05 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 419 (3): 603–610.
Article history
Received:
June 23 2008
Revision Received:
October 31 2008
Accepted:
November 05 2008
Accepted Manuscript online:
November 05 2008
Citation
Katja Lehmann, Jörg P. Müller, Bernhard Schlott, Philipp Skroblin, Dagmar Barz, Johannes Norgauer, Reinhard Wetzker; PI3Kγ controls oxidative bursts in neutrophils via interactions with PKCα and p47phox. Biochem J 1 May 2009; 419 (3): 603–610. doi: https://doi.org/10.1042/BJ20081268
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