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

J Biomed Sci. 2015 Mar 20;22(1):21. doi: 10.1186/s12929-015-0129-z.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics*
  • Acute-Phase Proteins / metabolism
  • Animals
  • Lipocalin-2
  • Lipocalins / genetics*
  • Lipocalins / metabolism
  • Mice
  • Neutrophils / metabolism*
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Phosphorylation
  • Protein Kinase C-delta / genetics*
  • Protein Kinase C-delta / metabolism
  • Reperfusion Injury / metabolism*


  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Lcn2 protein, mouse
  • Prkcd protein, mouse
  • Protein Kinase C-delta