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

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. © 2015 weng et al.; licensee biomed central.