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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References
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Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76–ADAP
TL;DR: The data indicate that TCR‐mediated ROS generation leads to SHP‐2 oxidation, which promotes T‐cell adhesion through effects on an SLP‐76‐dependent signaling pathway to integrin activation.
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Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons.
TL;DR: It is demonstrated that during oxidative stress, ERK-directed phosphatases of both the serine/threonine- and tyrosine-directed classes are selectively and reversibly inhibited via a mechanism that is dependent upon the oxidation of cysteine thiols.
Cysteine S-Nitrosylation Protects Protein-tyrosine Phosphatase 1B against Oxidation-induced
Yi-Yun Chen,Hsing-Mao Chu,Kuan-Ting Pan,Chun-Hung Teng,Danny-Ling Wang,Kay-Hooi Khoo,Tzu-Ching Meng +6 more
TL;DR: Findings suggest that S-nitrosylation might prevent PTPs from permanent inactivation caused by oxidative stress and increase the level of cellular NO by pretreating cells with an NO donor or by activating ectopically expressed NO synthase inhibited reactive oxygen species-induced irreversible oxidation of endogenous PTP1B.
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The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling.
Jaeyul Kwon,Jaeyul Kwon,Kristen E. Shatynski,Haiyan Chen,Stanislas Morand,Xavier De Deken,Françoise Miot,Thomas L. Leto,Mark S. Williams +8 more
TL;DR: Activation of Duox1, downstream of proximal TCR signals, generates H2O2 that acts in a positive feedback loop to enhance and sustain further TCR signaling, suggesting that ROS are functionally important in nonphagocytic cells of the immune system.
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Electrostatic Evaluation of the Signature Motif (H/V)CX5R(S/T) in Protein−Tyrosine Phosphatases†
TL;DR: The results indicate that the architecture of the (H/V)CX5R(S/T) loop has a major impact on the low pKa of the active cysteine, which is an important part of the consensus sequence.