S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation.
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Yamaguchi F, Umeda Y, Shimamoto S, Tsuchiya M, Tokumitsu H, Tokuda M, Kobayashi R
S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation.
J Biol Chem. 2012 Apr 20;287(17):13787-98. doi: 10.1074/jbc.M111.329771. Epub 2012 Mar 7.
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22399290 [View in PubMed]
- Abstract
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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.