S-Nitrosylation of p47phox enhances phosphorylation by casein kinase 2

Abstract

Objectives: Leukocyte NADPH oxidase, which is active in neutrophils, is a membrane-bound enzyme that catalyzes the reduction of oxygen to O₂^? by using NADPH as an electron donor. Previously, we reported that casein kinase 2 (CK2), a ubiquitous and highly conserved Ser/Thr kinase, is responsible for p47^phox phosphorylation and that phosphorylation of p47^phox by CK2 regulates the deactivation of NADPH oxidase.

Methods: Here, we report that the residue Cys¹⁹⁶ of p47^phox is a target of S-nitrosylation by S-nitrosothiol and peroxynitrite and that this modification enhanced phosphorylation of p47^phox by CK2. Results: S-Nitrosylated p47^phox enhanced CK2 b subunit binding, presumably due to alterations in protein conformation.

Discussion: Taken together, we propose that S-nitrosylation of p47^phox regulates the deactivation of NADPH oxidase via enhancement of p47^phox phosphorylation by CK2