Protein tyrosine phosphorylation and reversible oxidation: two cross-talking posttranslation modifications.
In addition to protein phosphorylation, redox-dependent posttranslational modification of proteins is emerging as a key signaling system, conserved throughout evolution, and influencing many aspects of cellular homeostasis. Recent data have provided new insight about the interplay between phosphorylation- and redox-dependent signaling, and reactive oxygen species have been included among intracellular signal transducers of growth factor and extracellular matrix receptors. Both tyrosine phosphorylation and thiol oxidation are reversible and dynamic, and this review will particularly focus on the cross-talk between these posttranslational protein regulatory means. Although these modifications share their reversibility, their effects on enzymatic activity of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) may be even opposite. Indeed, while tyrosine phosphorylation is frequently correlated to enzyme activation, thiol oxidation leads to inactivation of PTPs and to superactivation of PTKs. Several papers describe that both these modifications occur during the same input, (i.e., cell proliferation and motility induced by numerous growth factors and cytokines). The review will discuss several aspects of phosphorylation\oxidation interplay, describing both convergent and divergent features of the integrated and coordinated function of PTPs and PTKs during signaling.
Chiarugi
Paola
P
Department of Biochemical Sciences, University of Florence Center for Research, Transfer and High Education, Florence, Italy. paola.chiarugi@unifi.it
Buricchi
Francesca
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation
D000975:Antioxidants; D008024:Ligands; D017382:Reactive Oxygen Species; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases