PI3Kγ controls oxidative bursts in neutrophils via interactions with PKCα and p47phox

被引：30

作者：

Lehmann, Katia ^{[2
]}

Mueller, Joerg R. ^{[1
]}

Schlott, Bernhard ^{[3
]}

Skroblin, Philipp ^{[1
]}

Barz, Dagmar ^{[4
]}

Norgauer, Johannes ^{[2
]}

Wetzker, Reinhard ^{[1
]}

机构：

[1] Univ Jena, Ctr Mol Biomed, Inst Mol Cell Biol, Jena, Germany

[2] Univ Jena, Dept Dermatol, Jena, Germany

[3] Fritz Lipmann Inst eV, Leibniz Inst Age Res, Jena, Germany

[4] Univ Jena, Inst Transfus Med, Jena, Germany

来源：

BIOCHEMICAL JOURNAL | 2009年 / 419卷

关键词：

neutrophil; phosphoinositide 3-kinase gamma (PI3K gamma); protein kinase C alpha (PKC alpha); protein kinase; reactive oxygen species; PHOSPHOINOSITIDE 3-KINASE GAMMA; PROTEIN-KINASE-C; G-BETA-GAMMA; ACTIVATION; PHOSPHORYLATION; INFLAMMATION; SUBUNIT; ROLES; SITES; PI3K;

D O I：

10.1042/BJ20081268

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：603 / 610

页数：8

共 28 条

[1]

ABO A, 1992, J BIOL CHEM, V267, P16767

[2]

Adomeit A, 1999, MOL CELL BIOL, V19, P5289

[3] Differential regulation of lipid and proteins kinase activities of phosphoinositide 3-kinase γ in vitro [J].