Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers

This review focuses on the chemistry of the reversible oxidation of those thiolates, with a particular emphasis on the critical thiolate found in protein tyrosine phosphatases as an example

Henry Jay Forman

2004

Scholarcy highlights

  • Except for the role of NO in the activation of guanylate cyclase, which is well established, the involvement of reactive oxygen species and reactive nitrogen species in signal transduction remains controversial, despite a large body of evidence suggestive of their participation in a variety of signaling pathways
  • The involvement of free radicals in biology was assumed for many years to be restricted to damaging reactions, the discovery of the endogenous generation of NO in mammalian systems and the finding that this small, freely diffusing, chemically unique species participates in specific signal transduction pathways represented an important new paradigm and expanded views of the possible nature of cell communication and/or signaling processes
  • Because disulfide exchange is relatively slow for a biological reaction, even when GSH is dissociated to the thiolate, we propose that reduction of PrxVI-SSG requires an enzyme-catalyzed reaction with GSH
  • The discovery that ROS and RNS can act as signaling molecules has spurred further studies of their possible targets, and, as shown in this review, redox thiol chemistry has taken center stage
  • As only those proteins with cysteines in the thiolate form significantly react with low concentrations of H2O2 or ┬ĚNO-derived species, one can postulate that the number of potential targets is limited, thereby providing specificity
  • Meng et al showed that only the pool of Src homology phosphatase-2 associated with the PDGF receptor was reversibly inhibited by H2O2 produced upon receptor binding, indicating that localization of SHP-2 close to the membrane where a putative oxidase is more likely to be present played a critical role in this signaling pathway
  • Protein-protein interactions through the scaffolding proteins PSD95 and CAPON are essential to the regulation of the NMDA class of glutamate receptor via S-nitrosylation

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