Tyrosine Phosphorylation Modulates Peroxiredoxin-2 Activity in Normal and Diseased Red Cells

摘要: Peroxiredoxin-2 (Prx2) is the third most abundant cytoplasmic protein in red blood cells. Prx2 belongs to a well-known family of antioxidants, peroxiredoxins (Prxs), that are widely expressed mammalian typical, homodimeric, 2-Cys Prx uses two cysteine residues accomplish task detoxifying vast range organic peroxides, H2O2, and peroxynitrite. Although progress has been made on functional characterization Prx2, much still remains be investigated post-translational changes. Here, we first show Tyrosine (Tyr) phosphorylated by Syk cells exposed oxidation induced diamide. We identified Tyr-193 both recombinant native from as specific target Syk. Bioinformatic analysis suggests phosphorylation allows conformational change more favorable for its peroxidase activity. Indeed, Syk-induced Tyr enhances vitro activity, but also contributes translocation membrane The biologic importance phospho-Prx2 further supported data mouse model humanized sickle cell disease (SCD). SCD globally distributed, hereditary disorder, characterized severe due pathologic hemoglobin. Tyr-phosphorylated bound increased activity when compared healthy erythrocytes. Collectively, our highlight novel link between redox related signaling function normal diseased