title: Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN‑45 gastric carcinoma cells.
abstract: S100 proteins bind to numerous target proteins, as well as other S100 proteins and activate signaling cascades. S100 proteins can be modified by various post-translational modifications, such as phosphorylation, methylation and acetylation. In addition, oxidation is important for modulating their activities. Previous studies have shown that S100A1 interacts with S100A4 in vitro and in vivo. Due to this potential cross‑talk among the S100 proteins, the aim of the present study was to examine whether S100A4 modulates the activity of S100A1. S100A4 was readily oxidized and formed disulfide-linked dimers and oligomers. Although non-oxidized S100A4 bound to protein phosphatase 5 (PP5), the Cu-oxidized S100A4 failed to bind PP5. Instead, the Cu-oxidized S100A4 directly interacted with S100A1 and prevented PP5 activation. Hydrogen peroxide induced S100A4 oxidation in MKN-45 gastric adenocarcinoma cells and decreased S100A1‑PP5 interaction, resulted in the inhibition of PP5 activation by S100A1. These data indicate that oxidized S100A4 regulates PP5 activity in a unique manner under oxidative stress conditions.
authors.affiliation: Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Department of Cell Physiology, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Yamaguchi
authors.affiliation: Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimamoto
authors.affiliation: Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
authors.affiliation: Department of Cell Physiology, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Department of Signal Transduction Sciences, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000388:Air; D001667:Binding, Competitive / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003300:Copper / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D020349:Surface Plasmon Resonance
chemical_list: D004220:Disulfides; D009687:Nuclear Proteins; D016877:Oxidants; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C110294:S100A1 protein; C077591:S100A4 protein, human; D003300:Copper; D006861:Hydrogen Peroxide; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5