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
Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases.
TL;DR: These regulatory principles are reviewed, existing biologics and proteinaceous compounds that affect PTP activity are discussed, and future opportunities to drug PTPs via these regulatory concepts are mentioned.
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Benzoquinone, a leukemogenic metabolite of benzene, catalytically inhibits the protein tyrosine phosphatase PTPN2 and alters STAT1 signaling
Romain Duval,Linh-Chi Bui,Cécile Mathieu,Qing Nian,Jérémy Berthelet,Ximing Xu,Iman Haddad,Joëlle Vinh,Jean-Marie Dupret,Florent Busi,Fabien Guidez,Christine Chomienne,Fernando Rodrigues-Lima +12 more
TL;DR: It is shown here that 1,4-benzoquinone directly impairs PTPN2 activity and covalently modifies key signaling enzymes, implicating it in benzene-induced malignant blood diseases.
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Proteinase-activated receptor 1- and 4-promoted migration of Hep3B hepatocellular carcinoma cells depends on ROS formation and RTK transactivation.
Franziska Mußbach,Petra Henklein,Martin Westermann,Utz Settmacher,Frank-D. Böhmer,Roland Kaufmann +5 more
TL;DR: The data indicate that PAR1 and PAR4 activate common promigratory signalling pathways in Hep3B liver carcinoma cells including activation of the receptor tyrosine kinases Met and PDGFR, the formation of ROS and the inactivation of PTP1B.
Journal ArticleDOI
Isoliquiritigenin impairs insulin signaling and adipocyte differentiation through the inhibition of protein-tyrosine phosphatase 1B oxidation in 3T3-L1 preadipocytes
TL;DR: Findings show that the anti-oxidant capacity of ISL attenuates insulin IR/PI3K/AKT signaling through inhibition of PTP1B oxidation, and ultimately attenuated insulin-induced adipocyte differentiation of 3T3-L1 cells.
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Oxovanadium-based inhibitors can drive redox-sensitive cytotoxicity in neuroblastoma cells and synergise strongly with buthionine sulfoximine
Owen Clark,Inhye Park,Alessia Di Florio,Ann-Christin Cichon,Sarah Rustin,Roman Jugov,Ruhina Maeshima,Andrew W. Stoker +7 more
TL;DR: In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic, indicating that BMOV action is sensitive to cytoplasmic redox and thiol status.
References
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Protein Tyrosine Phosphatases in the Human Genome
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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.