Regulation of Cys-Based Protein Tyrosine Phosphatases Via Reactive Oxygen and Nitrogen Species in Mast Cells and Basophils

Abstract

Activation of mast cells and basophils is accompanied by the production of reactive oxygen and nitrogen species that regulate diverse signaling pathways leading to the release of inflammatory mediators and production of a variety of cytokines. Although the functional pathways of reactive oxygen and nitrogen species in vivo are not completely understood, some novel metabolic pathways can be envisioned based on recent findings that protein tyrosine phosphatases can be regulated by reversible oxidation. In this review, we describe major sources and targets of reactive oxide and nitrogen species in mast cells and basophils. Direct and indirect regulations of class I and II Cys-based protein tyrosine phosphatases (LMW-PTP, PTEN, PTP-PEST, SHP-2, PTP1B, PTPalpha, PTPepsilon, DEP-1, TC45, SHP-1, HePTP and LAR) are discussed. The combined data highlight the role of redox-regulated protein tyrosine phosphatases as targets in the development of new ways of therapeutic intervention in allergies and inflammatory diseases.

Genetic Screening for Synthetic Lethal Partners of Polynucleotide Kinase/Phosphatase: Potential for Targeting SHP-1–Depleted Cancers

“…It has been observed previously that SHP-1 depletion causes an increase in ROS production in human umbilical vein endothelial cells through its negative regulation of NAD(P)H-oxidasedependent superoxide production (28). Furthermore, SHP-1, in common with many other protein-tyrosine phosphatases, is susceptible to oxidation of key cysteine residues in its catalytic domain by ROS, including those generated by ionizing radiation (47,48). Our data (Fig.…”

Aryl hydrocarbon receptor controls murine mast cell homeostasis

“…[18][19][20][21][31][32][33] Herein, mast cells treated with AhR ligands showed increased oxidation of SHP-2, but not the highly homologous SHP-1, and reduced phosphatase activity. This selective oxidation may be due to different spatial orientation of the active-site cysteines in relation to positively charged residues (arginine) in the active-site pocket of the 2 phosphatases 34 or due to the specific subcellular location of individual PTP, where localized production of ROS and oxidation occurs.…”

Mitochondrial Reactive Oxygen Species Regulate Transforming Growth Factor-β Signaling

“…Many of the Smad-independent signaling pathways can be activated by intracellular reactive oxygen species (ROS) 2 (7). For example, kinase signaling can be prolonged by the ROS-mediated inactivation of phosphatases (8). Several groups of investigators have reported that NOX4 (NADPH oxidase 4) is induced by TGF-␤ to generate intracellular ROS, which are required for the conversion of lung, kidney, and cardiac fibroblasts into a myofibroblast phenotype (9 -11).…”