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Review
. 2008;40(11):2358-62.
doi: 10.1016/j.biocel.2007.08.010. Epub 2007 Aug 30.

Protein phosphatase 5

Terry D Hinds Jr  1 , Edwin R Sánchez
Affiliations
Review

Protein phosphatase 5

Terry D Hinds Jr et al. Int J Biochem Cell Biol. 2008.

Abstract

Protein phosphatase 5 (PP5) is a unique member of the PPP family of serine/threonine phosphatases based on the presence of tetratricopeptide repeat (TPR) domains within its structure. Since its discovery, PP5 has been implicated in wide ranging cellular processes, including MAPK-mediated growth and differentiation, cell cycle arrest and DNA damage repair via the p53 and ATM/ATR pathways, regulation of ion channels via the membrane receptor for atrial natriuretic peptide, the cellular heat shock response as mediated by heat shock transcription factor, and steroid receptor signaling, especially glucocorticoid receptor (GR). Given this diversity of effects, the recent development of viable PP5-deficient mice was surprising and suggests that PP5 is a modulatory, rather than essential, factor in phosphorylation pathways. Here, we review the signaling involvement of PP5 in light of new findings and relate these activities to the structural features of the protein.

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Figures

Fig. 1
Fig. 1
Diagrammatic representation of PP5 and its isoforms. See text for description of the functional domains and sites.
Fig. 2
Fig. 2
Model of PP5 actions on glucocorticoid receptor (GR). In most cells at least a fraction of GR/HSP90 heterocomplexes contain PP5 as the TPR protein component. In response to hormone, several well-documented events take place: 1) dissociation of GR from the heterocomplex, 2) dimerization of GR and binding to chromatin at gene promoters, and 3) hyperphosphorylation of GR, particularly residues S203, S211 and S226 (phopho-serines are in blue) of the AF-1 domain. It is now known that phosphorylation is required for maximal GR transciptional activity and that PP5 contributes to GR dephosphorylation at the indicated residues. We therefore propose that the main function of PP5 is to reset the phosphorylation state of GR, most likely during GR recycling to the cytoplasm and at de novo synthesis (not shown). It is also possible that GR hyperphosphorylation may increase as a consequence of PP5 release, in addition to active phosphorylation by kinases. PP5 may also contribute to GR action by altering its ability to bind hormone and to translocate to the nucleus (not shown).
See this image and copyright information in PMC

References

    1. Becker W, Kentrup H, Klumpp S, Schultz JE, Joost HG. Molecular cloning of a protein serine/threonine phosphatase containing a putative regulatory tetratricopeptide repeat domain. J Biol Chem. 1994;269:22586–22592. - PubMed
    1. Chen MS, Silverstein AM, Pratt WB, Chinkers M. The tetratricopeptide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant. J Biol Chem. 1996;271:32315–32320. - PubMed
    1. Chen MX, Cohen PT. Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain. FEBS Lett. 1997;400:136–140. - PubMed
    1. Chen MX, McPartlin AE, Brown L, Chen YH, Barker HM, Cohen PT. A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus. EMBO J. 1994;13:4278–4290. - PMC - PubMed
    1. Chinkers M. Targeting of a distinctive protein-serine phosphatase to the protein kinase-like domain of the atrial natriuretic peptide receptor. Proc Natl Acad Sci U S A. 1994;91:11075–11079. - PMC - PubMed

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