title: Reversible oxidation of PRL family protein-tyrosine phosphatases.
abstract: Recent studies have revealed that reactive oxygen species (ROS) are actively generated in cells and function as second messengers to mediate physiological intracellular signaling. ROS exert their effects on intracellular signaling via ROS effector proteins, which are sensitively and reversibly oxidized by ROS. Among various ROS effector proteins, the protein tyrosine phosphatase (PTP) family is of special interest. In the catalytic pocket, PTP proteins commonly possess a highly reactive cysteine (Cys) residue, which is susceptible to oxidation by ROS. Phosphatase of regenerating liver (PRL) belongs to the PTP family and is oxidized by ROS to form an intramolecular disulfide bond. In general, disulfide bonds in proteins can be reduced in cells with the help of various reducing enzymes, which enables the reversible redox regulation of PRL proteins. In the case of PRL proteins, thioredoxin-related protein 32 specifically catalyzes the reducing reaction, indicating the importance of redox regulation for ROS effector proteins.
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Funato
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: hmiki@biken.osaka-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miki
mesh_terms: D001681:Biological Assay; D020134:Catalytic Domain; D003545:Cysteine / Q000737:chemistry; D010084:Oxidation-Reduction; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D017382:Reactive Oxygen Species; D011505:Protein-Tyrosine Kinases; D003545:Cysteine
keywords: 5,5′-dithiobis-2-nitrobenzoic acid; Cys; DTNB; DTT; GSH; IPTG; MAP kinase phosphatase; MKP; N-ethlymaleimide; NADPH; NEM; PIP(3); PMSF; PRL; PRX; PTEN; PTP; PTP1B; ROS; TNFα; TRP14; TRP32; TRX; TRX reductase; TRX related protein 14; TRX related protein 32; TrxR; cysteine; dithiothreitol; glutathione; isopropyl-β-d-thiogalactopyranoside; nicotinamide adenine dinucleotide phosphate; peroxiredoxin; phenylmethylsulfonyl fluoride; phosphatase and tensin homolog deleted from chromosome 10; phosphatase of regenerating liver; phosphatidylinositol (3,4,5)-trisphosphate; protein tyrosine phosphatase; protein-tyrosine phosphatase 1B; reactive oxygen species; thioredoxin; tumor-necrosis factor α