S100 proteins modulate protein phosphatase 5 function: A link between Ca 2+ signal transduction and protein dephosphorylation

Fuminori Yamaguchi, Yoshinori Umeda, Seiko Shimamoto, Mitsumasa Tsuchiya, Hiroshi Tokumitsu, Masaaki Tokuda, Ryoji Kobayashi

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13787-13798
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number17
DOIs
Publication statusPublished - Apr 20 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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