Regulation of protein tyrosine phosphatases by reversible oxidation
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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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.
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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.
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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.