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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.

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Modulation of Ca2+ signaling by antiapoptotic Bcl-2 versus Bcl-xL: From molecular mechanisms to relevance for cancer cell survival.

TL;DR: In this article , the authors discuss the similarities and divergences between Bcl2 and Bcl-xL regarding Ca2+ homeostasis and IP3R modulation from both a molecular and a functional point of view, with particular emphasis on cancer cell death resistance mechanisms.
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Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation

- 19 May 2022 - 
TL;DR: In this paper , a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of the protein by forming a disulfide with the catalytic C227 residue, was found to have an increased severity in the development of T-cell-dependent autoimmunity.
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The physiological concentration of ferrous iron (II) alters the inhibitory effect of hydrogen peroxide on CD45, LAR and PTP1B phosphatases

TL;DR: It is found that the higher concentrations of ferrous iron (II) increase the inactivation of CD45, LAR and PTP1B phosphatase caused by hydrogen peroxide, but the addition of the physiological concentration (500 nM) offerrous iron has even a slightly preventive effect on theosphatase activity against hydrogenperoxide.
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Regulation of C1-Ten protein tyrosine phosphatase by p62/SQSTM1-mediated sequestration and degradation.

TL;DR: It is shown that p62 sequestrates C1-Ten into puncta, making C 1-Ten diffuse into the cytoplasm upon p62 depletion, and a role for p62 as a physiological regulator of C2-Ten is supported.
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.
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Protein Tyrosine Phosphatases in the Human Genome

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.
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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.
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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.
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