title: Redox regulation of protein kinases.
abstract: Reactive oxygen species (ROS) have been long regarded as by-products of a cascade of reactions stemming from cellular oxygen metabolism, which, if they accumulate to toxic levels, can have detrimental effects on cellular biomolecules. However, more recently, the recognition of ROS as mediators of cellular communications has led to their classification as signalling mediators in their own right. The prototypic redox-regulated targets downstream of ROS are the protein tyrosine phosphatases, and the wealth of research that has focused on this area has come to shape our understanding of how redox-signalling contributes to and facilitates protein tyrosine phosphorylation signalling cascades. However, it is becoming increasingly apparent that there is more to this system than simply the negative regulation of protein tyrosine phosphatases. Identification of redox-sensitive kinases such as Src led to the slow emergence of a role for redox regulation of tyrosine kinases. A flow of evidence, which has increased exponentially in recent times as a result of the development of new methods for the detection of oxidative modifications, demonstrates that, by concurrent oxidative activation of tyrosine kinases, ROS fine tune the duration and amplification of the phosphorylation signal. A more thorough understanding of the complex regulatory mechanism of redox-modification will allow targeting of both the production of ROS and their downstream effectors for therapeutic purposes. The present review assesses the most relevant recent literature that demonstrates a role for kinase regulation by oxidation, highlights the most significant findings and proposes future directions for this crucial area of redox biology.
authors: Tumour Biology Laboratory, Biochemistry Department, Bioscience Research Institute, University College Cork, Ireland.
authors: Aoife
authors: A
authors: Corcoran
authors: Thomas G
authors: TG
authors: Cotter
mesh_terms: D004789:Enzyme Activation; D006801:Humans; D010084:Oxidation-Reduction; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; D019061:src-Family Kinases