Redox regulation of protein kinase signaling

Reversible protein phosphorylation, mediated by reciprocal actions of protein kinases and phosphatases, represents a major mode of posttranslational regulation of protein function in all organisms. During the past 20years, it has become clear that protein phosphorylation is subject to oxidative mechanisms, which not only can inhibit major classes of protein phosphatase, particularly tyrosine phosphatases, but also can directly regulate various protein kinases as well as recognition of phosphorylated proteins, both positively and negatively. Such redox-based regulation typically involves reversible oxidation of conserved cysteine residues, although other oxidative modifications are also involved. The diverse modes of orthogonal regulation of protein phosphorylation by such reversible oxidative events indicate an intricate relationship between redox-dependent signaling mechanisms and protein kinase signaling pathways, especially in aerobic life. Dysregulation of such redox-dependent regulatory mechanisms during conditions of oxidative stress may contribute to abnormal protein phosphorylation and development of disease.