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

34 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
Externally publishedYes

Fingerprint

Signal transduction
S100 Proteins
Signal Transduction
Proteins
MAP Kinase Kinase Kinase 5
protein phosphatase 5
Phosphopeptides
Phosphorylation
Phosphoprotein Phosphatases
COS Cells
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

S100 proteins modulate protein phosphatase 5 function : A link between Ca 2+ signal transduction and protein dephosphorylation. / Yamaguchi, Fuminori; Umeda, Yoshinori; Shimamoto, Seiko; Tsuchiya, Mitsumasa; Tokumitsu, Hiroshi; Tokuda, Masaaki; Kobayashi, Ryoji.

In: Journal of Biological Chemistry, Vol. 287, No. 17, 20.04.2012, p. 13787-13798.

Research output: Contribution to journalArticle

Yamaguchi, Fuminori ; Umeda, Yoshinori ; Shimamoto, Seiko ; Tsuchiya, Mitsumasa ; Tokumitsu, Hiroshi ; Tokuda, Masaaki ; Kobayashi, Ryoji. / S100 proteins modulate protein phosphatase 5 function : A link between Ca 2+ signal transduction and protein dephosphorylation. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 17. pp. 13787-13798.
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