Regulation of protein tyrosine phosphatases by reversible oxidation
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TLDR
The role of PTP oxidation for physiological signalling processes as well as in different pathologies is described on the basis of well-investigated examples and criteria to establish the causal involvement of P TP oxidation in a given process are proposed.Abstract:
Oxidation of the catalytic cysteine of protein-tyrosine phosphatases (PTP), which leads to their reversible inactivation, has emerged as an important regulatory mechanism linking cellular tyrosine phosphorylation and signalling by reactive-oxygen or -nitrogen species (ROS, RNS). This review focuses on recent findings about the involved pathways, enzymes and biochemical mechanisms. Both the general cellular redox state and extracellular ligand-stimulated ROS production can cause PTP oxidation. Members of the PTP family differ in their intrinsic susceptibility to oxidation, and different types of oxidative modification of the PTP catalytic cysteine can occur. The role of PTP oxidation for physiological signalling processes as well as in different pathologies is described on the basis of well-investigated examples. Criteria to establish the causal involvement of PTP oxidation in a given process are proposed. A better understanding of mechanisms leading to selective PTP oxidation in a cellular context, and finding ways to pharmacologically modulate these pathways are important topics for future research.read more
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Journal ArticleDOI
In Vitro Activity Assays to Quantitatively Assess the Endogenous Reversible Oxidation State of Protein Tyrosine Phosphatases in Cells.
TL;DR: Assays that measure the endogenous activity of specific PTPs that become transiently inactivated in cells exposed to growth factors are presented in order to assess the inactivation and the reactivation of P TPs targeted by cellular oxidants in signal transduction.
Journal ArticleDOI
Role of Reactive Oxygen Species in the Cytotoxicity of Arsenic Trioxide and Pamidronate for Human Prostate Cancer Cells.
TL;DR: These experiments demonstrate additive or synergistic cell killing by the ARS/PAM combination in DU-145 or PC-3 cells and suggest that enhanced antitumor activity may be related to alterations in receptor tyrosine kinase signaling that occur, in part, due to ROS-mediated PTPase inhibition.
Book ChapterDOI
Redox Regulation of PTPs in Metabolism: Focus on Assays
Yang Xu,Benjamin G. Neel +1 more
TL;DR: ROS regulation of PTPs is reviewed, focusing on existing assays and new approaches to identify and quantify PTP oxidation, which represents a key challenge to understanding the role of P TPs and redox regulation in physiology and pathology.
Posted ContentDOI
FGF2-induced Redox Signaling: A Mechanism Regulating Pyruvate Dehydrogenase Driven Histone Acetylation and NANOG Upregulation
P. Fojtı́k,Martin Šenfluk,Katerina Holomková,Anton Salykin,Jana Gregorová,P. J. H. Smak,Ondřej Peš,Jan Raška,Monika Stetkova,Petr Skládal,Miroslava Sedláčková,Aleš Hampl,Dáša Bohačiaková,Stjepan Uldrijan,Vladimír Rotrekl +14 more
TL;DR: This article showed that pyruvate dehydrogenase (PDH) is an essential metabolic switch and a bottleneck for the glycolytic production of acetyl-CoA, and showed that PDP1 is sensitive to reactive oxygen species-mediated inactivation, leading to the downregulation of H3 pan acetylation and NANOG levels.
References
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Journal ArticleDOI
Reconciling the chemistry and biology of reactive oxygen species
TL;DR: This review examines how target selectivity and antioxidant effectiveness vary for different oxidants and highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.
Journal ArticleDOI
Protein Tyrosine Phosphatases in the Human Genome
Andres Alonso,Joanna Sasin,Nunzio Bottini,Ilan Friedberg,Iddo Friedberg,Andrei L. Osterman,Adam Godzik,Tony Hunter,Jack E. Dixon,Tomas Mustelin +9 more
TL;DR: The set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase (PTP) families are presented and the role of these enzymes in human disease will be discussed.
Journal ArticleDOI
Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases
TL;DR: It is shown that TNFalpha-induced ROS, whose accumulation is suppressed by mitochondrial superoxide dismutase, cause oxidation and inhibition of JNK-inactivating phosphatases by converting their catalytic cysteine to sulfenic acid, which results in sustained JNK activation, which is required for cytochrome c release and caspase 3 cleavage.
Journal ArticleDOI
Protein tyrosine phosphatases: from genes, to function, to disease
TL;DR: Recent breakthroughs in understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease are described.
Journal ArticleDOI
Hydrogen Peroxide Sensing and Signaling
TL;DR: The molecular mechanisms by which hydrogen peroxide is sensed and the increasing evidence that antioxidant enzymes play multiple, key roles as sensors and regulators of signal transduction in response to hydrogen peroxy are discussed.