Abstract
The oxidation of cysteine thiol side chains by hydrogen peroxide to afford protein sulfenyl modifications is an important mechanism in signal transduction. In addition, aberrant protein sulfenylation contributes to a range of human pathologies, including cancer. Efforts to elucidate the roles of protein sulfenylation in physiology and disease have been hampered by the lack of techniques to probe these modifications in native environments with molecular specificity. In this review, we trace the history of chemical and biological methods that have been developed to detect protein sulfenylation and illustrate how a recent cell-permeable chemical reporter, DYn-2, has been used to detect and identify intracellular targets of endogenous H2 O2 during growth factor signaling, including the epidermal growth factor receptor. The array of new tools and methods discussed herein enables the discovery of new biological roles for cysteine sulfenylation in human health and disease.