title: Identification of lipocalin-2 as a PKCδ phosphorylation substrate in neutrophils.
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.
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. yweng@kent.edu.
authors.forename: Yi-Chinn
authors.initials: YC
authors.lastname: Weng
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. gwang7@kent.edu.
authors.forename: Guona
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of California, San Francisco, CA, 94608, USA. romessing@austin.utexas.edu.|Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. romessing@austin.utexas.edu.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
authors.affiliation: Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, OH, 44224, USA. wchou2@kent.edu.|Department of Neurology, University of California, San Francisco, CA, 94608, USA. wchou2@kent.edu.
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Chou
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; C497259:Prkcd protein, mouse; D051745:Protein Kinase C-delta