NO Means No and Yes: Regulation of Cell Signaling by Protein Nitrosylation

Protein nitrosylation is emerging as a key mechanism by which nitric oxide regulates cell signaling. Nitrosylation is the binding of a NO group to a metal or thiol (-SH) on a peptide or protein. Like phosphorylation, nitrosylation is a precisely targeted and rapidly reversible posttranslational modification that allows cells to flexibly and specifically respond to changes in their environment. An increasing number of proteins have been identified whose activity is regulated by intracellular nitrosylation. This review focuses on proteins regulated by endogenous nitrosylation, the chemistry underlying nitrosylation, the specificity and reversibility of nitrosylation reactions, methods to detect protein nitrosylation, and the role of coordinated protein nitrosylation/denitrosylation in cell signaling.