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
Citations
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Book ChapterDOI
Redox regulation of protein tyrosine phosphatases: methods for kinetic analysis of covalent enzyme inactivation.
Zachary D. Parsons,Kent S. Gates +1 more
TL;DR: In this article, methods for quantitative analysis of covalent inactivation of protein tyrosine phosphatases by small molecules are discussed. But, the authors do not consider the effects of small molecules on the protein itself.
Journal ArticleDOI
NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1α and p27Kip1 expression in malignant melanoma and other human tumors.
Smitha Antony,Guojian Jiang,Yongzhong Wu,Jennifer L. Meitzler,Hala R. Makhlouf,Diana C. Haines,Donna Butcher,Dave S.B. Hoon,Jiuping Ji,Yiping Zhang,Agnes Juhasz,Jiamo Lu,Han Liu,Iris Dahan,Mariam M. Konaté,Krishnendu Roy,James H. Doroshow +16 more
TL;DR: It is suggested that NOX5 expression in human UACC‐257 melanoma cells could contribute to cell proliferation due, in part, to the generation of high local concentrations of extracellular ROS that modulate multiple pathways that regulate HIF‐1α and networks that signal through Akt/GSK3β/p27Kip1.
Journal ArticleDOI
Acute and long-term effects of arsenite in HepG2 cells: modulation of insulin signaling
Ingrit Hamann,Kerstin Petroll,Xiaoqing Hou,Anwar Anwar-Mohamed,Ayman O.S. El-Kadi,Lars-Oliver Klotz,Lars-Oliver Klotz +6 more
TL;DR: Arsenite perturbs cellular signaling pathways involved in fuel metabolism: it impairs cellular responsiveness toward insulin, while at the same time stimulating insulin-like signaling to attenuate the expression of genes involved in glucose metabolism and the release of the hepatokine SelP, which is known to modulate peripheral insulin sensitivity.
Journal ArticleDOI
Bidentate inhibitors of protein tyrosine phosphatases.
TL;DR: Bidentate inhibitors are small-molecular-weight compounds with the ability to bind to both the active site and a non-conserved secondary phosphate binding site that were initially discovered in protein tyrosine phosphatase 1B, and, hence, most of the bidentate inhibitor reported in this review are PTP1B inhibitors.
Journal ArticleDOI
New Strategy for Reversible Modulation of Protein Activity through Site-Specific Conjugation of Small Molecule and Polymer
TL;DR: A new strategy for accurate and reversible modulation of protein activity via simple conjugation of the sulfhydryl modifier and polymer with the introduced Cys residue in protein was developed in this study.
References
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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.