Format

Send to

Choose Destination
J Biomed Sci. 2015 Mar 20;22:21. doi: 10.1186/s12929-015-0129-z.

Identification of lipocalin-2 as a PKCδ phosphorylation substrate in neutrophils.

Author information

1
Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. yweng@kent.edu.
2
Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. gwang7@kent.edu.
3
Department of Neurology, University of California, San Francisco, CA, 94608, USA. romessing@austin.utexas.edu.
4
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. romessing@austin.utexas.edu.
5
Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. wchou2@kent.edu.
6
Department of Neurology, University of California, San Francisco, CA, 94608, USA. wchou2@kent.edu.

Abstract

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 chemical-genetics approach to identify PKCδ substrates in neutrophils.

RESULTS:

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.

CONCLUSIONS:

These findings suggest that PKCδ phosphorylates LCN2 and mediates its release from neutrophils during ischemia-reperfusion injury.

PMID:
25890235
PMCID:
PMC4396066
DOI:
10.1186/s12929-015-0129-z
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center