title: S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation.
abstract: PP5 is a unique member of serine/threonine phosphatases comprising a regulatory tetratricopeptide repeat (TPR) domain and functions in signaling pathways that control many cellular responses. We reported previously that Ca(2+)/S100 proteins directly associate with several TPR-containing proteins and lead to dissociate the interactions of TPR proteins with their client proteins. Here, we identified protein phosphatase 5 (PP5) as a novel target of S100 proteins. In vitro binding studies demonstrated that S100A1, S100A2, S100A6, and S100B proteins specifically interact with PP5-TPR and inhibited the PP5-Hsp90 interaction. In addition, the S100 proteins activate PP5 by using a synthetic phosphopeptide and a physiological protein substrate, Tau. Overexpression of S100A1 in COS-7 cells induced dephosphorylation of Tau. However, S100A1 and permanently active S100P inhibited the apoptosis signal-regulating kinase 1 (ASK1) and PP5 interaction, resulting the inhibition of dephosphorylation of phospho-ASK1 by PP5. The association of the S100 proteins with PP5 provides a Ca(2+)-dependent regulatory mechanism for the phosphorylation status of intracellular proteins through the regulation of PP5 enzymatic activity or PP5-client protein interaction.
authors.affiliation: Department of Cell Physiology, Kagawa University Faculty of Medicine, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Yamaguchi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Umeda
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimamoto
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tokuda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002522:Chlorocebus aethiops; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D009418:S100 Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020349:Surface Plasmon Resonance / Q000379:methods; D016875:tau Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009418:S100 Proteins; C110294:S100A1 protein; C103003:S100P protein, human; D016875:tau Proteins; C021240:tissue-factor-pathway inhibitor 2; D005982:Glutathione Transferase; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5; D002118:Calcium