- 作者: Yi-Chinn Weng, Guona Wang, Robert O Messing, Wen-Hai Chou
- 作者服務機構: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent , OH, USA
- 中文摘要: --
- 英文摘要:
Background:
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 chemicalgenetics approach to identify PKCδ substrates in neutrophils.
Results:
We recently generated knock-in mice endogenously expressing analog-specific PKCδ (ASPKCδ) 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.
Conclusions:
These findings suggest that PKCδ phosphorylates LCN2 and mediates its release from neutrophils during ischemia-reperfusion injury. - 中文關鍵字: --
- 英文關鍵字: PKC, Stroke, Neutrophil, Lipocalin-2, Phosphorylation