Identification of lipocalin-2 as a PKCδ phosphorylation substrate in neutrophils.
Identification of lipocalin-2 as a PKCδ phosphorylation substrate in neutrophils.
复制标题
将Lipocalin-2鉴定为中性粒细胞中的PKCδ磷酸化底物。
DOI：
10.1186/s12929-015-0129-z
复制
发表时间：
2015-03-20
影响因子：
11
通讯作者：
Chou WH
中科院分区：
文献类型：
--
作者：
Weng YC;Wang G;Messing RO;Chou WH
中性粒细胞表达的PKCδ参与促进缺血性卒中后再灌注损伤为了了解PKCδ的分子和细胞作用，我们采用化学遗传学方法来鉴定中性粒细胞中的PKCδ底物。我们最近产生了内源性表达类似物特异性PKCδ（AS-PKCδ）的敲入小鼠，该小鼠可以利用ATP类似物作为磷酸盐供体。使用从基因敲入小鼠中分离的中性粒细胞，我们鉴定了几种PKCδ底物，其中之一是脂质运载蛋白-2（LCN 2），这是一种铁结合蛋白，可以通过降低细胞内铁浓度引发细胞凋亡。我们发现PKCδ在T115磷酸化LCN 2，并且这种磷酸化在Prkcd−/−小鼠中减少。PKCδ与LCN 2共定位于静息和刺激的中性粒细胞中。PKCδ基因敲除小鼠脑缺血后中性粒细胞释放LCN 2减少。这些结果表明，PKCδ磷酸化LCN 2，并介导其释放从中性粒细胞在缺血再灌注损伤。
PKCδ expressed in neutrophils is implicated in promoting reperfusion injury after ischemic stroke. To understand the molecular and cellular actions of PKCδ, we employed a chemical-genetics approach to identify PKCδ substrates in neutrophils. We recently generated knock-in mice endogenously expressing analog-specific PKCδ (AS-PKCδ) that can utilize ATP analogs as phosphate donors. Using neutrophils isolated from the knock-in mice, we identified several PKCδ substrates, one of which was lipocalin-2 (LCN2), which is an iron-binding protein that can trigger apoptosis by reducing intracellular iron concentrations. We found that PKCδ phosphorylated LCN2 at T115 and this phosphorylation was reduced in Prkcd−/− mice. PKCδ colocalized with LCN2 in resting and stimulated neutrophils. LCN2 release from neutrophils after cerebral ischemia was reduced in PKCδ null mice. These findings suggest that PKCδ phosphorylates LCN2 and mediates its release from neutrophils during ischemia-reperfusion injury.
登录
查看更多内容
影响因子：
15.9
作者：
Chou, WH;Choi, DS;Messing, RO
通讯作者：
Messing, RO
影响因子：
21.3
作者：
Cohen, P
通讯作者：
Cohen, P
影响因子：
2.9
作者：
Falke, P;Elneihoum, AM;Ohlsson, K
通讯作者：
Ohlsson, K
影响因子：
64.5
作者：
Devireddy, LR;Gazin, C;Green, MR
通讯作者：
Green, MR
DOI：
10.1523/jneurosci.3156-08.2008
发表时间：
2008-11-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Choi DS;Wei W;Deitchman JK;Kharazia VN;Lesscher HM;McMahon T;Wang D;Qi ZH;Sieghart W;Zhang C;Shokat KM;Mody I;Messing RO
通讯作者：
Messing RO