磷脂酰肌醇-3激酶γ通过与蛋白激酶Cα和p47吞噬细胞氧化酶相互作用来控制中性粒细胞的氧化爆发。
PI3Kgamma controls oxidative bursts in neutrophils via interactions with PKCalpha and p47phox.
作者信息
Lehmann Katja, Müller Jörg P, Schlott Bernhard, Skroblin Philipp, Barz Dagmar, Norgauer Johannes, Wetzker Reinhard
机构信息
Department of Dermatology, Friedrich Schiller University, Jena, Germany.
出版信息
Biochem J. 2009 May 1;419(3):603-10. doi: 10.1042/BJ20081268.
Neutrophils release reactive oxygen species (ROS) as part of the innate inflammatory immune response. Phosphoinositide 3-kinase gamma (PI3Kgamma), 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 PI3Kgamma 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 PI3Kgamma with protein kinase Calpha (PKCalpha). Specific inhibition of PI3Kgamma suppresses fMLP-mediated activation of PKCalpha activity and ROS production, suggesting that the protein kinase activity of PI3Kgamma is involved. Our data suggest that the direct interaction of PI3Kgamma with PKCalpha forms a discrete regulatory module of fMLP-dependent ROS production in neutrophils.
中性粒细胞释放活性氧（ROS）作为先天性炎症免疫反应的一部分。由细菌肽N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）诱导的磷酸肌醇3激酶γ（PI3Kγ）已被确定为ROS产生的重要细胞内介质。然而，将PI3Kγ与NADPH氧化酶的ROS合成联系起来的复杂信号反应尚未详细描述。我们发现fMLP激活中性粒细胞会触发PI3Kγ与蛋白激酶Cα（PKCα）的结合。PI3Kγ的特异性抑制可抑制fMLP介导的PKCα活性激活和ROS产生，表明PI3Kγ的蛋白激酶活性参与其中。我们的数据表明，PI3Kγ与PKCα的直接相互作用形成了中性粒细胞中fMLP依赖性ROS产生的离散调节模块。
Zotero 插件