PTPs versus PTKs: the redox side of the coin.
The phosphorylation of tyrosine, and to a lesser extent threonine and serine, plays a key role in the regulation of signal transduction during a plethora of eukaryotic cell functions, including cell activation, cell-cycle progression, cytoskeletal rearrangement and cell movement, differentiation, apoptosis and metabolic homeostasis. In vivo, tyrosine phosphorylation is reversible and dynamic; the phosphorylation states are governed by the opposing activities of protein tyrosine kinases (PTKs)2 and protein tyrosine phosphatases (PTPs). Reactive oxygen species (ROS) act as cellular messengers in cellular processes such as mitogenic signal transduction, gene expression, regulation of cell proliferation, senescence and apoptosis. Redox regulated proteins include PTPs and PTKs, although with opposite regulation of enzymatic activity. Transient oxidation of thiols in PTPs leads to their inactivation by the formation of either an intramolecular S-S bridge or a sulfenyl-amide bond. Conversely, oxidation of PTKs leads to their activation, either by direct SH modification or, indirectly, by concomitant inhibition of PTPs that guides to sustained activation of PTKs. This review focuses on the redox regulation of both PTPs and PTKs and the interplay of their specular regulation.
Chiarugi
Paola
P
Department of Biochemical Sciences, University of Florence, viale Morgagni 50, 50134, Firenze, Italy. paola.chiarugi@unifi.it
D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000502:physiology; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases