A Large-Scale Quantitative Proteomic Approach To Identifying Sulfur Mustard-Induced Protein Phosphorylation Cascades

Sulfur mustard [SM, bis-(2-chloroethyl) sulfide] is a potent alkylating agent and chemical weapon. While there are no effective treatments for SM-induced injury, current research focuses on understanding the molecular changes upon SM exposure. Indeed, efforts that seek a more comprehensive analysis of proteins and post-translational modifications are critical for understanding SM-induced toxicity on a more global scale. Furthermore, these studies can uncover proteins previously uncharacterized in SM-exposed cells, which in turn leads to potential targets for therapeutic intervention. Here, we apply a quantitative proteomic approach termed stable isotope-labeling with amino acids in cell culture combined with immobilized metal affinity chromatography to study the large-scale protein phosphorylation changes resulting from SM exposure in a human keratinocyte cell culture model. This resulted in the characterization of over 2300 nonredundant phosphorylation sites, many of which exhibit altered levels in respo...