1932

Abstract

Protein serine/threonine phosphatases (PPPs) are ancient enzymes, with distinct types conserved across eukaryotic evolution. PPPs are segregated into types primarily on the basis of the unique interactions of PPP catalytic subunits with regulatory proteins. The resulting holoenzymes dock substrates distal to the active site to enhance specificity. This review focuses on the subunit and substrate interactions for PPP that depend on short linear motifs. Insights about these motifs from structures of holoenzymes open new opportunities for computational biology approaches to elucidate PPP networks. There is an expanding knowledge base of posttranslational modifications of PPP catalytic and regulatory subunits, as well as of their substrates, including phosphorylation, acetylation, and ubiquitination. Cross talk between these posttranslational modifications creates PPP-based signaling. Knowledge of PPP complexes, signaling clusters, as well as how PPPs communicate with each other in response to cellular signals should unlock the doors to PPP networks and signaling “clouds” that orchestrate and coordinate different aspects of cell physiology.

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2018-06-20
2024-05-29
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Literature Cited

  1. 1.  Fischer EH, Krebs EG 1955. Conversion of phosphorylase b to phosphorylase a in muscle extracts. J. Biol. Chem. 216:121–32
    [Google Scholar]
  2. 2.  Sutherland EW, Wosilait WD 1955. Inactivation and activation of liver phosphorylase. Nature 175:169–70
    [Google Scholar]
  3. 3.  Salazar C, Höfer T 2009. Multisite protein phosphorylation – from molecular mechanisms to kinetic models. FEBS J 276:3177–98
    [Google Scholar]
  4. 4.  Hunter T, Sefton BM 1980. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. PNAS 77:1311–15
    [Google Scholar]
  5. 5.  Hunter T. 2009. Tyrosine phosphorylation: thirty years and counting. Curr. Opin. Cell Biol. 21:140–46
    [Google Scholar]
  6. 6.  Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C et al. 2006. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635–48
    [Google Scholar]
  7. 7.  Hanks S, Hunter T 1995. The eukaryotic protein kinase superfamily: kinase catalytic domain structure and classification. FASEB J 9:576–96
    [Google Scholar]
  8. 8.  Madsen NB, Kasvinsky PJ, Fletterick RJ 1978. Allosteric transitions of phosphorylase a and the regulation of glycogen metabolism. J. Biol. Chem. 253:9097–101
    [Google Scholar]
  9. 9.  Roach PJ, Takeda Y, Larner J 1976. Rabbit skeletal muscle glycogen synthase. I. Relationship between phosphorylation state and kinetic properties. J. Biol. Chem. 251:1913–19
    [Google Scholar]
  10. 10.  Witters LA, Watts TD, Daniels DL, Evans JL 1988. Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. PNAS 85:5473–77
    [Google Scholar]
  11. 11.  Beg ZH, Stonik JA, Brewer HB 1978. 3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation. PNAS 75:3678–82
    [Google Scholar]
  12. 12.  Roskoski R. 2005. Src kinase regulation by phosphorylation and dephosphorylation. Biochem. Biophys. Res. Commun. 331:1–14
    [Google Scholar]
  13. 13.  Sebastian B, Kakizuka A, Hunter T 1993. Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. PNAS 90:3521–24
    [Google Scholar]
  14. 14.  Yaffe MB, Smerdon SJ 2001. Phosphoserine/threonine binding domains: You can't pSERious?. Structure 9:R33–38
    [Google Scholar]
  15. 15.  Reinhardt HC, Yaffe MB 2013. Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response. Nat. Rev. Mol. Cell Biol. 14:563–80
    [Google Scholar]
  16. 16.  Kleinman LB, Maiwald T, Conzelman H, Lauffenburger DA, Sorger PK 2011. Rapid phospho-turnover by receptor tyrosine kinases impacts downstream signaling and drug binding. Mol. Cell 43:723–37
    [Google Scholar]
  17. 17.  Blazek M, Santisteban TS, Zengerle R, Meier M 2015. Analysis of fast protein phosphorylation kinetics in single cells on a microfluidic chip. Lab Chip 15:726–34
    [Google Scholar]
  18. 18.  Gomez-Uribe C, Verghese GC, Mirny LA 2007. Operating regimes of signaling cycles: statics, dynamics, and noise filtering. PLOS Comput. Biol. 3:e246
    [Google Scholar]
  19. 19.  Lemmon MA, Freed DM, Schlessinger J, Kiyatkin A 2016. The dark side of cell signaling: positive roles for negative regulators. Cell 164:1172–84
    [Google Scholar]
  20. 20.  Heinrich R, Neel BG, Rapoport TA 2002. Mathematical models of protein kinase signal transduction. Mol. Cell 9:957–70
    [Google Scholar]
  21. 21.  Gelens L, Qian J, Bollen M, Saurin AT 2018. The importance of kinase-phosphatase integration: lessons from mitosis. Trends Cell Biol 28:6–21
    [Google Scholar]
  22. 22.  Ingebritsen TS, Cohen P 1983. Protein phosphatases: properties and role in cellular regulation. Science 221:331–38
    [Google Scholar]
  23. 23.  Shi Y. 2009. Serine/threonine phosphatases: mechanism through structure. Cell 139:468–84
    [Google Scholar]
  24. 24.  Cohen PT. 2002. Protein phosphatase 1 – targeted in many directions. J. Cell Sci. 115:241–56
    [Google Scholar]
  25. 25.  Virshup DM, Shenolikar S 2009. From promiscuity to precision: protein phosphatases get a makeover. Mol. Cell 33:537–45
    [Google Scholar]
  26. 26.  Wlodarchak N, Xing Y 2016. PP2A as a master regulator of the cell cycle. Crit. Rev. Biochem. Mol. Biol. 51:162–84
    [Google Scholar]
  27. 27.  Sharma K, D'Souza RCJ, Tyanova S, Schaab C, Wisniewski JR et al. 2014. Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8:1583–94
    [Google Scholar]
  28. 28.  Das AK, Helps NR, Cohen PT, Barford D 1996. Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 Å resolution. EMBO J 15:6798–809
    [Google Scholar]
  29. 29.  Tanoue K, Miller-Jenkins LM, Durell SR, Debnath S, Sakai H et al. 2013. Binding of a third metal ion by the human phosphatases PP2Cα and Wip1 is required for phosphatase activity. Biochemistry 52:5830–43
    [Google Scholar]
  30. 30.  Su J, Schlicker C, Forchhammer K 2011. A third metal is required for catalytic activity of the signal-transducing protein phosphatase M tPphA. J. Biol. Chem. 286:13481–88
    [Google Scholar]
  31. 31.  Singh A, Pandey A, Srivastava AK, Tran LS, Pandey GK 2016. Plant protein phosphatases 2C: from genomic diversity to functional multiplicity and importance in stress management. Crit. Rev. Biotechnol. 36:1023–35
    [Google Scholar]
  32. 32.  Lammers T, Levi S 2008. Role of type 2C protein phosphatases in growth regulation and in cellular stress signaling. Crit. Rev. Biochem. Mol. Biol. 42:437–61
    [Google Scholar]
  33. 33.  Seifried A, Schultz J, Gohla A 2013. Human HAD phosphatases: structure, mechanism, and roles in health and disease. FEBS J 280:549–71
    [Google Scholar]
  34. 34.  Mayfield JE, Burkholder NT, Zhang YJ 2016. Dephosphorylating eukaryotic RNA polymerase II. Biochim. Biophys. Acta 1864:372–87
    [Google Scholar]
  35. 35.  Andreeva AV, Kutuzov MA 2009. PPEF/PP7 protein Ser/Thr phosphatases. Cell. Mol. Life Sci. 66:3103–10
    [Google Scholar]
  36. 36.  Chen MJ, Dixon JE, Manning G 2017. Genomics and evolution of protein phosphatases. Sci. Signal. 10:eaag1796
    [Google Scholar]
  37. 37.  Uhrig RG, Kerk D, Moorhead GB 2013. Evolution of bacterial-like phosphoprotein phosphatases in photosynthetic eukaryotes features ancestral mitochondrial or archaeal origin and possible lateral gene transfer. Plant Physiol 163:1829–43
    [Google Scholar]
  38. 38.  Zhang R, Ou H-Y, Zhang C-T 2004. DEG, a database of essential genes. Nucleic Acids Res. 32:D271–72
    [Google Scholar]
  39. 39.  Swingle M, Ni L, Honkanen RE 2007. Small molecule inhibitors of Ser/Thr phosphatases: specificity, use and common forms of abuse. Methods Mol. Biol. 365:23–38
    [Google Scholar]
  40. 40.  MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA 1990. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett 264:187–92
    [Google Scholar]
  41. 41.  Haystead TA, Sim AT, Carling D, Honnor RC, Tsukitani Y et al. 1989. Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism. Nature 337:78–81
    [Google Scholar]
  42. 42.  McConnell JL, Wadzinski BE 2009. Targeting protein serine/threonine phosphatases for drug development. Mol. Pharmacol. 75:1249–61
    [Google Scholar]
  43. 43.  Kao G, Tuck S, Baillie D, Sundaram MV 2004. C. elegans SUR-6/PR65 cooperates with LET-92/protein phosphatase 2A and promotes Raf activity independently of inhibitory Akt phosphorylation sites. Development 131:755–65
    [Google Scholar]
  44. 44.  Han X, Gomes JE, Birmingham CL, Pintard L, Sugimoto A, Mains PE 2009. The role of protein phosphatase 4 in regulating microtubule severing in the Caenorhabditis elegans embryo. Genetics 181:933–43
    [Google Scholar]
  45. 45.  Afshar K, Werner ME, Tse YC, Glotzer M, Gonczy P 2010. Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH-6 in one-cell stage C. elegans embryos. Development 137:237–47
    [Google Scholar]
  46. 46.  Bastians H, Ponstingl H 1996. The novel human protein serine/threonine phosphatase 6 is a functional homologue of budding yeast Sit4p and fission yeast ppe1, which are involved in cell cycle regulation. J. Cell Sci. 109:2865–74
    [Google Scholar]
  47. 47.  Morales-Johansson H, Puria R, Brautigan DL, Cardenas ME 2009. Human protein phosphatase PP6 regulatory subunits provide Sit4-dependent and rapamycin-sensitive sap function in Saccharomyces cerevisiae. PLOS ONE 4:e6331
    [Google Scholar]
  48. 48.  Fernandez-Sarabia MJ, Sutton A, Zhong T, Arndt KT 1992. SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1. Genes Dev 6:2417–28
    [Google Scholar]
  49. 49.  Goshima G, Iwasaki O, Obuse C, Yanagida M 2003. The role of Ppe1/PP6 phosphatase for equal chromosome segregation in fission yeast kinetochore. EMBO J 22:2752–63
    [Google Scholar]
  50. 50.  Yin D, Huang P, Wu J, Song H 2014. Drosophila protein phosphatase V regulates lipid homeostasis via the AMPK pathway. J. Mol. Cell. Biol. 6:100–2
    [Google Scholar]
  51. 51.  Mi J, Dziegielewski J, Bolesta E, Brautigan DL, Larner JM 2009. Activation of DNA-PK by ionizing radiation is mediated by protein phosphatase 6. PLOS ONE 4:e4395
    [Google Scholar]
  52. 52.  Douglas P, Zhong J, Ye R, Moorhead GB, Xu X, Lees-Miller SP 2010. Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX. Mol. Cell. Biol. 30:1368–81
    [Google Scholar]
  53. 53.  Zeng K, Bastos RN, Barr FA, Gruneberg U 2010. Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2. J. Cell Biol. 191:1315–32
    [Google Scholar]
  54. 54.  Rusin SF, Schlosser KA, Adamo ME, Kettenbach AN 2015. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells. Sci. Signal. 8:rs12
    [Google Scholar]
  55. 55.  Ohama T, Wang L, Griner EM, Brautigan DL 2013. Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions. BMC Cell Biol 14:42
    [Google Scholar]
  56. 56.  Steele FR, Washburn T, Rieger R, O'Tousa JE 1992. Drosophila retinal degeneration C (rdgC) encodes a novel serine/threonine protein phosphatase. Cell 69:669–76
    [Google Scholar]
  57. 57.  Lee SJ, Montell C 2001. Regulation of the rhodopsin protein phosphatase, RDGC, through interaction with calmodulin. Neuron 32:1097–106
    [Google Scholar]
  58. 58.  Ramulu P, Kennedy M, Xiong WH, Williams J, Cowan M et al. 2001. Normal light response, photoreceptor integrity, and rhodopsin dephosphorylation in mice lacking both protein phosphatases with EF hands (PPEF-1 and PPEF-2). Mol. Cell. Biol. 21:8605–14
    [Google Scholar]
  59. 59.  Sun X, Kang X, Ni M 2012. Hypersensitive to red and blue 1 and its modification by protein phosphatase 7 are implicated in the control of Arabidopsis stomatal aperture. PLOS Genet 8:e1002674
    [Google Scholar]
  60. 60.  Gibbons JA, Kozubowski L, Tatchell K, Shenolikar S 2007. Expression of human protein phosphatase-1 in Saccharomyces cerevisiae highlights the role of phosphatase isoforms in regulating eukaryotic functions. J. Biol. Chem. 282:21838–47
    [Google Scholar]
  61. 61.  Da Cruz e Silva EF, Hughes V, McDonald P, Stark MJ, Cohen PT 1991. Protein phosphatase 2Bw and protein phosphatase Z are Saccharomyces cerevisiae enzymes. Biochim. Biophys. Acta 1089:269–72
    [Google Scholar]
  62. 62.  Venturi GM, Bloecher A, Williams-Hart T, Tatchell K 2000. Genetic interactions between GLC7, PPZ1 and PPZ2 in Saccharomyces cerevisiae. Genetics 155:69–83
    [Google Scholar]
  63. 63.  García-Gimeno MA, Muñoz I, Ariño J, Sanz P 2003. Molecular characterization of Ypi1, a novel Saccharomyces cerevisiae type 1 protein phosphatase inhibitor. J. Biol. Chem. 278:47744–52
    [Google Scholar]
  64. 64.  Posas F, Bollen M, Stalmans W, Ariño J 1995. Biochemical characterization of recombinant yeast PPZ1, a protein phosphatase involved in salt tolerance. FEBS Lett 368:39–44
    [Google Scholar]
  65. 65.  Chen E, Choy MS, Petrényi K, Kónya Z, Erdődi F et al. 2016. Molecular insights into the fungus-specific serine/threonine protein phosphatase Z1 in Candida albicans. mBio 7:e00872–16
    [Google Scholar]
  66. 66.  Molero C, Casado C, Ariño J 2017. The inhibitory mechanism of Hal3 on the yeast Ppz1 phosphatase: a mutagenesis analysis. Sci. Rep. 7:8819
    [Google Scholar]
  67. 67.  Hurley TD, Yang J, Zhang L, Goodwin KD, Zou Q et al. 2007. Structural basis for regulation of protein phosphatase 1 by inhibitor-2. J. Biol. Chem. 282:28874–83
    [Google Scholar]
  68. 68.  Cohen PT. 1997. Novel protein serine/threonine phosphatases: variety is the spice of life. Trends Biochem. Sci. 22:245–51
    [Google Scholar]
  69. 69.  Vincent JB, Averill BA 1990. Sequence homology between purple acid phosphatases and phosphoprotein phosphatases. FEBS Lett 263:265–68
    [Google Scholar]
  70. 70.  Mitic N, Miraula M, Selleck C, Hadler KS, Uribe E et al. 2014. Catalytic mechanisms of metallohydrolyses containing two metal ions. Adv. Protein Chem. Struct. Biol. 97:49–81
    [Google Scholar]
  71. 71.  Griffith JP, Kim JL, Kim EE, Sintchak MD, Thomson JA et al. 1995. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell 82:507–22
    [Google Scholar]
  72. 72.  Nishito Y, Usui H, Shinzawa-Itoh K, Inoue R, Tanabe O et al. 1999. Direct metal analyses of Mn2+-dependent and -independent protein phosphatase 2A from human erythrocytes detect zinc and iron only in the Mn2+-independent one. FEBS Lett 447:29–33
    [Google Scholar]
  73. 73.  Egloff MP, Cohen PT, Reinemer P, Barford D 1995. Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate. J. Mol. Biol. 254:942–59
    [Google Scholar]
  74. 74.  Endo S, Conner JH, Forney B, Zhang L, Ingebritsen TS et al. 1997. Conversion of protein phosphatase 1 catalytic subunit to a Mn2+-dependent enzyme impairs its regulation by inhibitor-1. Biochemistry 36:6986–92
    [Google Scholar]
  75. 75.  Goldberg J, Huang HB, Kwon YG, Greengard P, Nairn AC, Kuriyan J 1995. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatse-1. Nature 376:745–53
    [Google Scholar]
  76. 76.  Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA et al. 1995. Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature 378:641–44
    [Google Scholar]
  77. 77.  Watanabe T, Huang HB, Horiuchi A, da Cruz e Silva EF, Hsieh-Wilson L et al. 2001. Protein phosphatase 1 regulation by inhibitors and targeting subunits. PNAS 98:3080–85
    [Google Scholar]
  78. 78.  Verbinnen I, Ferreira M, Bollen M 2017. Biogenesis and activity regulation of protein phosphatase 1. Biochem. Soc. Trans. 45:89–99
    [Google Scholar]
  79. 79.  Yang SD, Vandenheede JR, Merlevede W 1981. Identification of inhibitor-2 as the ATP-Mg-dependent protein phosphatase modulator. J. Biol. Chem. 256:10231–34
    [Google Scholar]
  80. 80.  Bollen M, Stalmans W 1992. The structure, role, and regulation of type 1 protein phosphatases. Crit. Rev. Biochem. Mol. Biol. 27:227–81
    [Google Scholar]
  81. 81.  Alessi DR, Street AJ, Cohen P, Cohen PT 1993. Inhibitor-2 functions like a chaperone to fold three expressed isoforms of mammalian protein phosphatase-1 into a conformation with the specificity and regulatory properties of the native enzyme. Eur. J. Biochem. 213:1055–66
    [Google Scholar]
  82. 82.  Cheng YL, Chen RH 2015. Assembly and quality control of the protein phosphatase 1 holoenzyme involves the Cdc48-Shp1 chaperone. J. Cell Sci. 128:1180–92
    [Google Scholar]
  83. 83.  Lesage B, Beullens M, Pedelini L, Garcia-Gimeno MA, Waelkens E et al. 2007. A complex of catalytically inactive protein phosphatase-1 sandwiched between Sds22 and inhibitor-3. Biochemistry 46:8909–19
    [Google Scholar]
  84. 84.  Löw C, Quistgaard EM, Kovermann M, Anandapadamanaban M, Balbach J, Nordlund P 2014. Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A. J. Biol. Chem. 395:881–89
    [Google Scholar]
  85. 85.  Lillo C, Kataya AR, Heidari B, Creighton MT, Nemie-Feyissa D et al. 2014. Protein phosphatases PP2A, PP4 and PP6: mediators and regulators in development and responses to environmental cues. Plant Cell Environ 37:2631–48
    [Google Scholar]
  86. 86.  Fellner T, Lackner DH, Hombauer H, Piribauer P, Mudrak I et al. 2003. A novel and essential mechanism determining specificity and activity of protein phosphatase 2A (PP2A) in vivo. Genes Dev 17:2138–50
    [Google Scholar]
  87. 87.  Guo F, Stanevich V, Wlodarchak N, Sengupta R, Jiang L et al. 2014. Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone. Cell Res 24:190–203
    [Google Scholar]
  88. 88.  Arsenault R, Griebel P, Napper S 2011. Peptide arrays for kinome analysis: new opportunities and remaining challenges. Proteomics 11:4595–609
    [Google Scholar]
  89. 89.  McNall SJ, Fischer EH 1988. Phosphorylase phosphatase. Comparison of active forms using peptide substrates. J. Biol. Chem. 263:1893–97
    [Google Scholar]
  90. 90.  Agostinis P, Goris J, Pinna LA, Marchiori F, Perich JW et al. 1990. Synthetic peptides as model substrates for the study of the specificity of the polycation-stimulated protein phosphatases. Eur. J. Biochem. 189:235–41
    [Google Scholar]
  91. 91.  Wegner AM, McConnell JL, Blakely RD, Wadzinski BE 2007. An automated fluorescence-based method for continuous assay of PP2A activity. Methods Mol. Biol. 365:61–69
    [Google Scholar]
  92. 92.  Oberoi J, Dunn DM, Woodford MR, Mariotti L, Schulman J et al. 2016. Structural and functional basis of protein phosphatase 5 substrate specificity. PNAS 113:9009–14
    [Google Scholar]
  93. 93.  Maynes JT, Bateman KS, Cherney MM, Das AK, Luu HA et al. 2001. Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1. J. Biol. Chem. 276:44078–82
    [Google Scholar]
  94. 94.  Kelker MS, Page R, Peti W 2009. Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors. J. Mol. Biol. 385:11–21
    [Google Scholar]
  95. 95.  Ingebritsen TS, Cohen P 1983. The protein phosphatases involved in cellular regulation. 1. Classification and substrate specificities. Eur. J. Biochem. 132:255–61
    [Google Scholar]
  96. 96.  Reinhart PH, Chung S, Martin BL, Brautigan DL, Levitan IB 1991. Modulation of calcium-activated potassium channels from rat brain by protein kinase A and phosphatase 2A. J. Neurosci. 11:1627–35
    [Google Scholar]
  97. 97.  DeFranco DB, Qi M, Borror KC, Garabedian MJ, Brautigan DL 1991. Protein phosphatase types 1 and/or 2A regulate nucleocytoplasmic shuttling of glucocorticoid receptors. Mol. Endocrinol. 5:1215–28
    [Google Scholar]
  98. 98.  Fernandez A, Brautigan DL, Mumby M, Lamb NJ 1990. Protein phosphatase type-1, not type-2A, modulates actin microfilament integrity and myosin light chain phosphorylation in living nonmuscle cells. J. Cell Biol. 111:103–12
    [Google Scholar]
  99. 99.  Ohama T, Wang L, Griner EM, Brautigan DL 2013. Protein Ser/Thr phosphatase-6 is required for maintenance of E-cadherin at adherens junctions. BMC Cell Biol 14:42
    [Google Scholar]
  100. 100.  Golden RJ, Chen B, Li T, Braun J, Manjunath H et al. 2017. An Argonaute phosphorylation cycle promotes microRNA-mediated silencing. Nature 542:197–202
    [Google Scholar]
  101. 101.  Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B et al. 2012. Attributes of short linear motifs. Mol. Biol. Syst. 8:268–81
    [Google Scholar]
  102. 102.  Davey NE, Cyert MS, Moses AM 2015. Short linear motifs – ex nihilo evolution of protein regulation. Cell Commun. Signal. 13:43–58
    [Google Scholar]
  103. 103.  Wu J, Liu J, Thompson I, Oliver CJ, Shenolikar S, Brautigan DL 1998. A conserved domain for glycogen binding in protein phosphatase-1 targeting subunits. FEBS Lett 439:185–91
    [Google Scholar]
  104. 104.  Egloff MP, Johnson DF, Moorhead G, Cohen PT, Cohen P, Barford D 1997. Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1. EMBO J 16:1876–87
    [Google Scholar]
  105. 105.  Heroes E, Lesage B, Gornemann J, Beullens M, Meervelt LV, Bollen M 2013. The PP1 binding code: a molecular-lego strategy that governs specificity. FEBS J 280:584–95
    [Google Scholar]
  106. 106.  Bollen M, Peti W, Ragusa MJ, Beullens M 2010. The extended PP1 toolkit: designed to create specificity. Trends Biochem. Sci. 35:450–58
    [Google Scholar]
  107. 107.  Ceulemans H, Stalmans W, Bollen M 2002. Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution. BioEssays 24:371–81
    [Google Scholar]
  108. 108.  Haesen D, Abbasi Asbagh L, Derua R, Hubert A, Schrauwen S et al. 2016. Recurrent PPP2R1A mutations in uterine cancer act through a dominant-negative mechanism to promote malignant cell growth. Cancer Res 76:5719–31
    [Google Scholar]
  109. 109.  Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J et al. 2008. A PP4-phosphatase complex dephosphorylates γ-H2AX generated during DNA replication. Mol. Cell 31:33–46
    [Google Scholar]
  110. 110.  Vincent A, Berthel E, Dacheux E, Magnard C, Venezia NL 2016. BRCA1 affects protein phosphatase 6 signalling through its interaction with ANKRD28. Biochem. J. 473:949–60
    [Google Scholar]
  111. 111.  Ramsey AJ, Chinkers M 2002. Identification of potential physiological activators of protein phosphatase 5. Biochemistry 41:5625–32
    [Google Scholar]
  112. 112.  Vaughan CK, Mollapour M, Smith JR, Truman A, Hu B et al. 2008. Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Mol. Cell 31:886–95
    [Google Scholar]
  113. 113.  Aitken A, Bilham T, Cohen P 1982. Complete primary structure of protein phosphatase inhibitor-1 from rabbit skeletal muscle. Eur. J. Biochem. 26:235–46
    [Google Scholar]
  114. 114.  Aitken A, Cohen P 1982. Isolation and characterisation of active fragments of protein phosphatase inhibitor-1 from rabbit skeletal muscle. FEBS Lett 147:54–58
    [Google Scholar]
  115. 115.  Endo S, Zhou X, Connor J, Wang B, Shenolikar S 1996. Multiple structural elements define the specificity of recombinant human inhibitor-1 as a protein phosphatase-1 inhibitor. Biochemistry 35:5220–28
    [Google Scholar]
  116. 116.  Kwon YG, Huang HB, Desdouits F, Girault JA, Greengard P, Nairn AC 1997. Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins. PNAS 94:3536–41
    [Google Scholar]
  117. 117.  Doherty MJ, Moorhead G, Morrice N, Cohen P, Cohen PT 1995. Amino acid sequence and expression of the hepatic glycogen-binding (GL)-subunit of protein phosphatase-1. FEBS Lett 375:294–98
    [Google Scholar]
  118. 118.  Terrak M, Kerff F, Langsetmo K, Tao T, Dominguez R 2004. Structural basis of protein phosphatase 1 regulation. Nature 429:780–84
    [Google Scholar]
  119. 119.  Ragusa MJ, Dancheck B, Critton DA, Nairn AC, Page R, Peti W 2010. Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites. Nat. Struct. Mol. Biol. 17:459–64
    [Google Scholar]
  120. 120.  O'Connell N, Nichols S, Heroes E, Beullens M, Bollen M et al. 2012. The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme. Structure 20:1746–56
    [Google Scholar]
  121. 121.  Choy MS, Hieke M, Kumar GS, Lewis GR, Gonzalez-DeWhitt KR et al. 2014. Understanding the antagonism of retinoblastoma protein dephosphorylation by PNUTS provides insights into the PP1 regulatory code. PNAS 111:4097–102
    [Google Scholar]
  122. 122.  Choy MS, Yusoff P, Lee IC, Newton JC, Goh CW et al. 2015. Structural and functional analysis of the GADD34:PP1 eIF2α phosphatase. Cell Rep 11:1885–91
    [Google Scholar]
  123. 123.  Kumar GS, Gokhan E, De Munter S, Bollen M, Vagnarelli P et al. 2016. The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism. eLife 5:e16539
    [Google Scholar]
  124. 124.  Choy MS, Page R, Peti W 2012. Regulation of protein phosphatase 1 by intrinsically disordered proteins. Biochem. Soc. Trans. 40:969–74
    [Google Scholar]
  125. 125.  Huang HB, Chen YC, Tsai LH, Wang H, Lin FM et al. 2000. Backbone 1H, 15N, and 13C resonance assignments of inhibitor-2 – a protein inhibitor of protein phosphatase-1. J. Biomol. NMR 17:359–60
    [Google Scholar]
  126. 126.  Hirschi A, Cecchini M, Steinhardt RC, Schamber MR, Dick FA, Rubin SM 2010. An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nat. Struct. Mol. Biol. 17:1051–57
    [Google Scholar]
  127. 127.  Rojas M, Vasconcelos G, Dever TE 2015. An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α. PNAS 112:E3466–75
    [Google Scholar]
  128. 128.  Grallert A, Boke E, Hagting A, Hodgson B, Connolly Y et al. 2015. A PP1-PP2A phosphatase relay controls mitotic progression. Nature 517:94–98
    [Google Scholar]
  129. 129.  Moorhead G, MacKintosh RW, Morrice N, Gallagher T, MacKintosh C 1994. Purification of type 1 protein (serine/threonine) phosphatases by microcystin-Sepharose affinity chromatography. FEBS Lett 356:46–50
    [Google Scholar]
  130. 130.  Campos M, Fadden P, Alms G, Qian Z, Haystead TA 1996. Identification of protein phosphatase-1-binding proteins by microcystin-biotin affinity chromatography. J. Biol. Chem. 271:28478–84
    [Google Scholar]
  131. 131.  Terry-Lorenzo RT, Inoue M, Connor JH, Haystead TA, Armbruster BN et al. 2000. Neurofilament-L is a protein phosphatase-1-binding protein associated with neuronal plasma membrane and post-synaptic density. J. Biol. Chem. 275:2439–46
    [Google Scholar]
  132. 132.  Trinkle-Mulcahy L, Andersen J, Lam YW, Moorhead G, Mann M, Lamond AI 2006. Repo-Man recruits PP1γ to chromatin and is essential for cell viability. J. Cell Biol. 172:679–92
    [Google Scholar]
  133. 133.  Moorhead GB, Trinkle-Mulcahy L, Nimick M, De Wever V, Campbell DG et al. 2008. Displacement affinity chromatography of protein phosphatase one (PP1) complexes. BMC Biochem 9:28
    [Google Scholar]
  134. 134.  Terry-Lorenzo RT, Elliot E, Weiser DC, Prickett TD, Brautigan DL, Shenolikar S 2002. Neurabins recruit protein phosphatase-1 and inhibitor-2 to the actin cytoskeleton. J. Biol. Chem. 277:46535–43
    [Google Scholar]
  135. 135.  Dancheck B, Ragusa MJ, Allaire M, Nairn AC, Page R, Peti W 2011. Molecular investigations of the structure and function of the protein phosphatase 1-spinophilin-inhibitor 2 heterotrimeric complex. Biochemistry 50:1238–46
    [Google Scholar]
  136. 136.  Stralfors P, Hiraga A, Cohen P 1985. The protein phosphatases involved in cellular regulation. Purification and characterization of the glycogen-bound form of protein phosphatase-1 from rabbit skeletal muscle. Eur. J. Biochem. 149:295–303
    [Google Scholar]
  137. 137.  Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S 2001. Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol. Cell. Biol. 21:6841–50
    [Google Scholar]
  138. 138.  Wang H, Brautigan DL 2002. A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2. J. Biol. Chem. 277:49605–12
    [Google Scholar]
  139. 139.  Eto M, Elliott E, Prickett TD, Brautigan DL 2002. Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation. J. Biol. Chem. 277:44013–20
    [Google Scholar]
  140. 140.  Pedelini L, Marquina M, Ariño J, Casamayor A, Sanz L et al. 2007. YPI1 and SDS22 proteins regulate the nuclear localization and function of yeast type 1 phosphatase Glc7. J. Biol. Chem. 282:3282–92
    [Google Scholar]
  141. 141.  Yan Z, Hsieh-Wilson L, Feng J, Tomizawa K, Allen PB et al. 1999. Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP-32 and spinophilin. Nat. Neurosci. 2:13–17
    [Google Scholar]
  142. 142.  Kelker MS, Dancheck B, Ju T, Kessler RP, Hudak J et al. 2007. Structural basis for spinophilin-neurabin receptor interaction. Biochemistry 46:2333–44
    [Google Scholar]
  143. 143.  Carmody LC, Baucum AJ, Bass MA, Colbran RJ 2008. Selective targeting of the γ1 isoform of protein phosphatase 1 to F-actin in intact cells requires multiple domains in spinophilin and neurabin. FASEB J 22:1660–71
    [Google Scholar]
  144. 144.  Terry-Lorenzo RT, Roadcap DW, Otsuka T, Blanpied TA, Zamorano PL et al. 2005. Neurabin/protein phosphatase-1 complex regulates dendritic spine morphogenesis and maturation. Mol. Biol. Cell 16:2349–62
    [Google Scholar]
  145. 145.  Greenberg CC, Danos AM, Brady MJ 2006. Central role for protein targeting to glycogen in the maintenance of cellular glycogen stores in 3T3-L1 adipocytes. Mol. Cell. Biol. 26:334–42
    [Google Scholar]
  146. 146.  Brush MH, Weiser DC, Shenolikar S 2003. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol. 23:1292–303
    [Google Scholar]
  147. 147.  Novoa I, Zeng H, Harding HP, Ron D 2001. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α. J. Cell Biol. 153:1011–22
    [Google Scholar]
  148. 148.  Yamashiro S, Yamakita Y, Totsukawa G, Goto H, Kaibuchi K et al. 2008. Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1. Dev. Cell 14:787–97
    [Google Scholar]
  149. 149.  Matsumura F, Yamakita Y, Yamashiro S 2011. Myosin phosphatase-targeting subunit 1 controls chromatid segregation. J. Biol. Chem. 286:10825–33
    [Google Scholar]
  150. 150.  Riedel CG, Katis VL, Katou Y, Mori S, Itoh T et al. 2006. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441:53–61
    [Google Scholar]
  151. 151.  Kruse T, Zhang G, Larsen MS, Lischetti T, Streicher W et al. 2013. Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. J. Cell Sci. 126:1086–92
    [Google Scholar]
  152. 152.  Terry-Lorenzo RT, Carmody LC, Voltz JW, Connor JH, Li S et al. 2002. The neuronal actin-binding proteins, neurabin I and neurabin II, recruit specific isoforms of protein phosphatase-1 catalytic subunits. J. Biol. Chem. 277:27716–24
    [Google Scholar]
  153. 153.  Hartshorne DJ, Ito M, Erdödi F 1998. Myosin light chain phosphatase: subunit composition, interactions and regulation. J. Muscle Res. Cell Motil. 19:325–41
    [Google Scholar]
  154. 154.  Eto M, Kirkbride J, Elliott E, Lo SH, Brautigan DL 2007. Association of the tensin N-terminal protein-tyrosine phosphatase domain with the alpha isoform of protein phosphatase-1 in focal adhesions. J. Biol. Chem. 282:17806–15
    [Google Scholar]
  155. 155.  Varmuza S, Jurisicova A, Okano K, Hudson J, Boekelheide K, Shipp EB 1999. Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cγ gene. Dev. Biol. 205:98–110
    [Google Scholar]
  156. 156.  Carmody LC, Bauman PA, Bass MA, Mavila N, DePaoli-Roach AA, Colbran RJ 2004. A protein phosphatase-1γ1 isoform selectivity determinant in dendritic spine-associated neurabin. J. Biol. Chem. 279:21714–23
    [Google Scholar]
  157. 157.  Kerk D, Bulgrien J, Smith DW, Barsam B, Veretnik S, Gribskov M 2002. The complement of protein phosphatase catalytic subunits encoded in the genome of Arabidopsis. Plant Physiol 129:908–25
    [Google Scholar]
  158. 158.  Reinke V, Smith HE, Nance J, Wang J, Van Doren C et al. 2000. A global profile of germline gene expression in C. elegans. Mol. Cell 6:605–16
    [Google Scholar]
  159. 159.  Adam C, Henn L, Miskei M, Erdelyi M, Friedrich P, Dombradi V 2010. Conservation of male-specific expression of novel phosphoprotein phosphatases in Drosophila. Dev. Genes Evol 220:123–28
    [Google Scholar]
  160. 160.  Carvalho AB, Dobo BA, Vibranovski MD, Clark AG 2001. Identification of five new genes on the Y chromosome of Drosophila melanogaster. PNAS 98:13225–30
    [Google Scholar]
  161. 161.  Cho US, Xu W 2007. Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature 445:53–57
    [Google Scholar]
  162. 162.  Xu Y, Xing Y, Chen Y, Chao Y, Lin Z et al. 2006. Structure of the protein phosphatase 2A holoenzyme. Cell 127:1239–51
    [Google Scholar]
  163. 163.  Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y 2008. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Mol. Cell 31:873–85
    [Google Scholar]
  164. 164.  Li X, Scuderi A, Letsou A, Virshup DM 2002. B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in Drosophila melanogaster. Mol. Cell. Biol 22:3674–84
    [Google Scholar]
  165. 165.  Kremmer E, Ohst K, Kiefer J, Brewis N, Walter G 1997. Separation of PP2A core enzyme and holoenzyme with monoclonal antibodies against the regulatory A subunit: abundant expression of both forms in cells. Mol. Cell. Biol. 17:1692–701
    [Google Scholar]
  166. 166.  Slupe AM, Merrill RA, Strack S 2011. Determinants for substrate specificity of protein phosphatase 2A. Enzyme Res 2011:398751
    [Google Scholar]
  167. 167.  Suijkerbuijk SJ, Vleugel M, Teixeira A, Kops GJ 2012. Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments. Dev. Cell 23:745–55
    [Google Scholar]
  168. 168.  Xu Z, Cetin B, Anger M, Cho US, Helmhart W et al. 2009. Structure and function of the PP2A-shugoshin interaction. Mol. Cell 35:426–41
    [Google Scholar]
  169. 169.  Wang X, Bajaj R, Bollen M, Peti W, Page R 2016. Expanding the PP2A interactome by defining a B56-specific SLiM. Structure 24:2174–81
    [Google Scholar]
  170. 170.  Wu CG, Chen H, Guo F, Yadav VK, Mcilwain SJ et al. 2017. PP2A-B′ holoenzyme substrate recognition, regulation and role in cytokinesis. Cell Discov 3:17027
    [Google Scholar]
  171. 171.  Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H et al. 2007. CIP2A inhibits PP2A in human malignancies. Cell 130:51–62
    [Google Scholar]
  172. 172.  Espert A, Uluocak P, Bastos RN, Mangat D, Graab P, Gruneberg U 2014. PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing. J. Cell Biol. 206:833–42
    [Google Scholar]
  173. 173.  Krystkowiak I, Davey NE 2017. SLiMSearch: a framework for proteome-wide discovery and annotation of functional modules in intrinsically disordered regions. Nucleic Acids Res 45:W464–69
    [Google Scholar]
  174. 174.  Davey NE, Seo MH, Yadav VK, Jeon J, Nim S et al. 2017. Discovery of short linear motif-mediated interactions through phage display of intrinsically disordered regions of the human proteome. FEBS J 284:485–98
    [Google Scholar]
  175. 175.  Hertz EPT, Kruse T, Davey NE, Blanca Lopez-Mendez BL, Sigursson JO et al. 2016. A conserved motif provides binding specificity to the PP2A-B56 phosphatase. Mol. Cell 63:686–95
    [Google Scholar]
  176. 176.  Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y 2008. Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation. Mol. Cell 31:873–85
    [Google Scholar]
  177. 177.  Li H, Rao A, Hogan PG 2011. Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol 21:91–103
    [Google Scholar]
  178. 178.  Aramburu J, Garcia-Cózar F, Raghavan A, Okamura H, Rao A, Hogan PG 1998. Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT. Mol. Cell 1:627–37
    [Google Scholar]
  179. 179.  Aramburu J, Yaffe MB, López-Rodríguez C, Cantley LC, Hogan PG, Rao A 1999. Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A. Science 285:2129–33
    [Google Scholar]
  180. 180.  Li H, Zhang L, Rao A, Harrison SC, Hogan PG 2007. Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction. J. Mol Biol. 369:1296–306
    [Google Scholar]
  181. 181.  Goldman A, Roy J, Bodenmiller B, Wanka S, Landry CR et al. 2014. The calcineurin signaling network evolves via conserved kinase–phosphatase modules that transcend substrate identity. Mol. Cell 55:422–35
    [Google Scholar]
  182. 182.  Roehrl MHA, Kang S, Aramburu J, Wagner G, Rao A, Hogan PG 2004. Selective inhibition of calcineurin-NFAT signaling by blocking protein–protein interaction with small organic molecules. PNAS 101:7554–59
    [Google Scholar]
  183. 183.  Grigoriu S, Bond R, Cossio P, Chen JA, Ly N et al. 2013. The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin. PLOS Biol 11:e1001492
    [Google Scholar]
  184. 184.  Huai Q, Kim HY, Liu Y, Zhao Y, Mondragon A et al. 2002. Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes. PNAS 99:12037–42
    [Google Scholar]
  185. 185.  Sheftic SR, Page R, Peti W 2016. Investigating the human calcineurin interaction network using the πϕLxVP SLiM. Sci. Rep. 6:38920
    [Google Scholar]
  186. 186.  Hosing AS, Valerie NC, Dziegielewski J, Brautigan DL, Larner JM 2012. PP6 regulatory subunit R1 is bidentate anchor for targeting protein phosphatase-6 to DNA-dependent protein kinase. J. Biol. Chem. 287:9230–39
    [Google Scholar]
  187. 187.  Dohadwala M, da Cruz e Silva EF, Hall FL, Williams RT, Carbonaro-Hall DA et al. 1994. Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases. PNAS 91:6408–12
    [Google Scholar]
  188. 188.  Kwon YG, Lee SY, Choi Y, Greengard P, Nairn AC 1997. Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase. PNAS 94:2168–73
    [Google Scholar]
  189. 189.  Schmitz MH, Held M, Janssens V, Hutchins JR, Hudecz O et al. 2010. Live-cell imaging RNAi screen identifies PP2A-B55α and importin-β1 as key mitotic exit regulators in human cells. Nat. Cell Biol. 12:886–93
    [Google Scholar]
  190. 190.  Chen J, Parsons S, Brautigan DL 1994. Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts. J. Biol. Chem. 269:7957–62
    [Google Scholar]
  191. 191.  Liu R, Zhou XW, Tanila H, Bjorkdahl C, Wang JZ et al. 2008. Phosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology. J. Cell. Mol. Med. 12:241–57
    [Google Scholar]
  192. 192.  Luo Y, Nie YJ, Shi HR, Ni ZF, Wang Q et al. 2013. PTPA activates protein phosphatase-2A through reducing its phosphorylation at tyrosine-307 with upregulation of protein tyrosine phosphatase 1B. Biochim. Biophys. Acta 1833:1235–43
    [Google Scholar]
  193. 193.  Khromov A, Choudhury N, Stevenson AS, Somlyo AV, Eto M 2009. Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction. J. Biol. Chem. 284:21569–79
    [Google Scholar]
  194. 194.  Walker KS, Watt PW, Cohen P 2000. Phosphorylation of the skeletal muscle glycogen-targetting subunit of protein phosphatase 1 in response to adrenaline in vivo. FEBS Lett 466:121–24
    [Google Scholar]
  195. 195.  Hubbard MJ, Cohen P 1989. Regulation of protein phosphatase-1G from rabbit skeletal muscle. 1. Phosphorylation by cAMP-dependent protein kinase at site 2 releases catalytic subunit from the glycogen-bound holoenzyme. Eur. J. Biochem. 186:701–9
    [Google Scholar]
  196. 196.  Kim YM, Watanabe T, Allen PB, Kim YM, Lee SJ et al. 2003. PNUTS, a protein phosphatase 1 (PP1) nuclear targeting subunit. Characterization of its PP1- and RNA-binding domains and regulation by phosphorylation. J. Biol. Chem. 278:13819–28
    [Google Scholar]
  197. 197.  Duan H, Wang C, Wang M, Gao X, Yan M, Akram S et al. 2016. Phosphorylation of PP1 regulator Sds22 by PLK1 ensures accurate chromosome segregation. J. Biol. Chem. 291:21123–36
    [Google Scholar]
  198. 198.  Zhou W, Jeyaraman K, Yusoff P, Shenolikar S 2013. Phosphorylation at tyrosine 262 promotes GADD34 protein turnover. J. Biol. Chem. 288:33146–55
    [Google Scholar]
  199. 199.  Kirchhefer U, Heinick A, König S, Kristensen T, Müller FU et al. 2014. Protein phosphatase 2A is regulated by protein kinase Cα (PKCα)-dependent phosphorylation of its targeting subunit B56α at Ser41. J. Biol. Chem. 289:163–76
    [Google Scholar]
  200. 200.  Ahn JH, McAvoy T, Rakhilin SV, Nishi A, Greengard P, Nairn AC 2007. Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56δ subunit. PNAS 104:2979–84
    [Google Scholar]
  201. 201.  Xu Z, Williams BR 2000. The B56α regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. Mol. Cell. Biol. 20:5285–89
    [Google Scholar]
  202. 202.  Letourneux C, Rocher G, Porteu F 2006. B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK. EMBO J 25:727–38
    [Google Scholar]
  203. 203.  Williams BC, Filter JJ, Blake-Hodek KA, Wadzinski BE, Fuda NJ et al. 2014. Greatwall-phosphorylated Endosulfine is both an inhibitor and a substrate of PP2A-B55 heterotrimers. eLife 3:e01695
    [Google Scholar]
  204. 204.  Filter JJ, Williams BC, Eto M, Shalloway D, Goldberg ML 2017. Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1). eLife 6:e24665
    [Google Scholar]
  205. 205.  Kim SS, Lee EH, Lee K, Jo SH, Seo SR 2015. PKA regulates calcineurin function through the phosphorylation of RCAN1: identification of a novel phosphorylation site. Biochem. Biophys. Res. Commun. 459:604–9
    [Google Scholar]
  206. 206.  Ruvolo PP. 2016. The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance. BBA Clin 6:87–99
    [Google Scholar]
  207. 207.  Longin S, Goris J 2006. Reversible methylation of protein phosphatase 2A. Enzymes 24:303–24
    [Google Scholar]
  208. 208.  De Baere I, Derua R, Janssens V, Van Hoof C, Waelkens E et al. 1999. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 38:16539–47
    [Google Scholar]
  209. 209.  Ogris E, Du X, Nelson KC, Mak EK, Yu XX et al. 1999. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. J. Biol. Chem. 274:14382–91
    [Google Scholar]
  210. 210.  Wei H, Ashby DG, Moreno CS, Ogris E, Yeong FM et al. 2001. Carboxymethylation of the PP2A catalytic subunit in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p. J. Biol. Chem. 276:1570–77
    [Google Scholar]
  211. 211.  Bryant JC, Westphal RS, Wadzinski BE 1999. Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Bα subunit. Biochem. J. 339:241–46
    [Google Scholar]
  212. 212.  Tolstykh T, Lee J, Vafai S, Stock JB 2000. Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits. EMBO J 19:5682–91
    [Google Scholar]
  213. 213.  Wu J, Tolstykh T, Lee J, Boyd K, Stock JB, Broach JR 2000. Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J 19:5672–81
    [Google Scholar]
  214. 214.  Yu XX, Du X, Moreno CS, Green RE, Ogris E et al. 2001. Methylation of the protein phosphatase 2A catalytic subunit is essential for association of Bα regulatory subunit but not SG2NA, striatin, or polyomavirus middle tumor antigen. Mol. Biol. Cell 12:185–99
    [Google Scholar]
  215. 215.  Janssens V, Longin S, Goris J 2008. PP2A holoenzyme assembly: in Cauda venenum (the sting is in the tail). Trends Biochem. Sci. 33:113–21
    [Google Scholar]
  216. 216.  Stanevich V, Zheng A, Guo F, Jiang L, Wlodarchak N, Xing Y 2014. Mechanisms of the scaffold subunit in facilitating protein phosphatase 2A methylation. PLOS ONE 9:e86955
    [Google Scholar]
  217. 217.  Hwang J, Lee JA, Pallas DC 2016. Leucine carboxyl methyltransferase 1 (LCMT-1) methylates protein phosphatase 4 (PP4) and protein phosphatase 6 (PP6) and differentially regulates the stable formation of different PP4 holoenzymes. J. Biol. Chem. 291:21008–19
    [Google Scholar]
  218. 218.  Dudiki T, Kadunganattil S, Ferrara JK, Kline DW, Vijayaraghavan S 2015. Changes in carboxy methylation and tyrosine phosphorylation of protein phosphatase PP2A are associated with epididymal sperm maturation and motility. PLOS ONE 10:e0141961
    [Google Scholar]
  219. 219.  Sents W, Meeusen B, Kalev P, Radaelli E, Sagaert X et al. 2017. PP2A inactivation mediated by PPP2R4 haploinsufficiency promotes cancer development. Cancer Res 77:6825–37
    [Google Scholar]
  220. 220.  Kaur A, Denisova OV, Qiao X, Jumppanen M, Peuhu E et al. 2016. PP2A inhibitor PME-1 drives kinase inhibitor resistance in glioma cells. Cancer Res 76:7001–11
    [Google Scholar]
  221. 221.  Chasseigneaux S, Clamagirand C, Huguet L, Gorisse-Hussonnois L, Rose C, Allinquant B 2014. Cytoplasmic SET induces tau hyperphosphorylation through a decrease of methylated phosphatase 2A. BMC Neurosci 15:82
    [Google Scholar]
  222. 222.  Hunter T. 2007. The age of crosstalk: phosphorylation, ubiquitination, and beyond. Mol. Cell 28:730–38
    [Google Scholar]
  223. 223.  Cuisset L, Tichonicky L, Delpech M 1998. A protein phosphatase is involved in the inhibition of histone deacetylation by sodium butyrate. Biochem. Biophys. Res. Commun. 246:760–64
    [Google Scholar]
  224. 224.  Edmondson DG, Davie JK, Zhou J, Mirnikjoo B, Tatchell K, Dent SY 2002. Site-specific loss of acetylation upon phosphorylation of histone H3. J. Biol. Chem. 277:29496–502
    [Google Scholar]
  225. 225.  Canettieri G, Morantte I, Guzmán E, Asahara H, Herzig S et al. 2003. Attenuation of a phosphorylation-dependent activator by an HDAC-PP1 complex. Nat. Struct. Biol. 10:175–81
    [Google Scholar]
  226. 226.  Brush MH, Guardiola A, Connor JH, Yao TP, Shenolikar S 2004. Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J. Biol. Chem. 279:7685–91
    [Google Scholar]
  227. 227.  Hu X, Lu X, Liu R, Ai N, Cao Z et al. 2014. Histone cross-talk connects protein phosphatase 1α (PP1α) and histone deacetylase (HDAC) pathways to regulate the functional transition of bromodomain-containing 4 (BRD4) for inducible gene expression. J. Biol. Chem. 289:23154–67
    [Google Scholar]
  228. 228.  Koshibu K, Gräff J, Beullens M, Heitz FD, Berchtold D et al. 2009. Protein phosphatase 1 regulates the histone code for long-term memory. J. Neurosci. 41:13079–89
    [Google Scholar]
  229. 229.  Wang W, Brautigan DL 2008. Phosphatase inhibitor 2 promotes acetylation of tubulin in the primary cilium of human retinal epithelial cells. BMC Cell Biol 9:62
    [Google Scholar]
  230. 230.  Joo EE, Yamada KM 2014. MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly. Nat. Commun. 5:3510
    [Google Scholar]
  231. 231.  Parra M, Mahmoudi T, Verdin E 2007. Myosin phosphatase dephosphorylates HDAC7, controls its nucleocytoplasmic shuttling, and inhibits apoptosis in thymocytes. Genes Dev 21:638–43
    [Google Scholar]
  232. 232.  Nunbhakdi-Craig V, Schuechner S, Sontag JM, Montgomery L, Pallas DC et al. 2007. Expression of protein phosphatase 2A mutants and silencing of the regulatory Bα subunit induce a selective loss of acetylated and detyrosinated microtubules. J. Neurochem. 101:959–71
    [Google Scholar]
  233. 233.  Weeks KL, Ranieri A, Karaś A, Bernardo BC, Ashcroft AS et al. 2017. β-Adrenergic stimulation induces histone deacetylase 5 (HDAC5) nuclear accumulation in cardiomyocytes by B55α-PP2A-mediated dephosphorylation. J. Am. Heart Assoc. 6:e004861
    [Google Scholar]
  234. 234.  Chen C, Wei X, Wang S, Jiao Q, Zhang Y et al. 2016. Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation. Biochim. Biophys. Acta 1863:1633–42
    [Google Scholar]
  235. 235.  Martin M, Potente M, Janssens V, Vertommen D, Twizere JC et al. 2008. Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis. PNAS 105:4727–32
    [Google Scholar]
  236. 236.  Mo F, Zhuang X, Liu X, Yao PY, Qin B et al. 2016. Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation. Nat. Chem. Biol. 12:226–32
    [Google Scholar]
  237. 237.  Togi S, Kamitani S, Kawakami S, Ikeda O, Muromoto R et al. 2009. HDAC3 influences phosphorylation of STAT3 at serine 727 by interacting with PP2A. Biochem. Biophys. Res. Commun. 379:616–20
    [Google Scholar]
  238. 238.  Zhang X, Ozawa Y, Lee H, Wen YD, Tan TH et al. 2005. Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes Dev 19:827–39
    [Google Scholar]
  239. 239.  Zhang T, Wang S, Lin Y, Xu W, Ye D et al. 2012. Acetylation negatively regulates glycogen phosphorylase by recruiting protein phosphatase 1. Cell Metab 15:75–87
    [Google Scholar]
  240. 240.  Prola A, Silva JP, Guilbert A, Lecru L, Piquereau J et al. 2017. SIRT1 protects the heart from ER stress-induced cell death through eIF2α deacetylation. Cell Death Differ 24:343–56
    [Google Scholar]
  241. 241.  Lee IC, Ho XY, George SE, Goh CW, Sundaram JR et al. 2017. Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1α complex to activate its deacetylase function. Cell Death Differ 25:255–67
    [Google Scholar]
  242. 242.  Chen Y, Zhao W, Yang JS, Cheng Z, Luo H et al. 2012. Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways. Mol. Cell. Proteom. 11:1048–62
    [Google Scholar]
  243. 243.  Komander D, Rape M 2012. The ubiquitin code. Annu. Rev. Biochem. 81:203–29
    [Google Scholar]
  244. 244.  Kwon YT, Ciechanover A 2017. The ubiquitin code in the ubiquitin-proteasome system and autophagy. Trends Biochem. Sci. 42:11873–86
    [Google Scholar]
  245. 245.  Zheng N, Shabek N 2017. Ubiquitin ligases: structure, function, and regulation. Annu. Rev. Biochem. 86:129–57
    [Google Scholar]
  246. 246.  Kim W, Bennett EJ, Huttlin EL, Guo A, Li J et al. 2011. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44:325–40
    [Google Scholar]
  247. 247.  Yau R, Rape M 2016. The increasing complexity of the ubiquitin code. Nat. Cell Biol. 18:579–86
    [Google Scholar]
  248. 248.  Swatek KN, Komander D 2016. Ubiquitin modifications. Cell Res 26:399–422
    [Google Scholar]
  249. 249.  Ohtake F, Tsuchiya H 2017. The emerging complexity of ubiquitin architecture. J. Biochem. 161:125–33
    [Google Scholar]
  250. 250.  Chen T, Zhou T, He B, Yu H, Guo X et al. 2014. mUbiSiDa: a comprehensive database for protein ubiquitination sites in mammals. PLOS ONE 9:e85744
    [Google Scholar]
  251. 251.  Ordureau A, Munch C, Harper JW 2015. Quantifying ubiquitin signaling. Mol. Cell 58:660–76
    [Google Scholar]
  252. 252.  Snyder PM. 2009. Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase Nedd4-2. Sci. Signal. 2:pe41
    [Google Scholar]
  253. 253.  Gallagher E, Gao M, Liu YC, Karin M 2006. Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change. PNAS 103:1717–22
    [Google Scholar]
  254. 254.  Cheng Q, Cross B, Li B, Chen L, Li Z, Chen J 2011. Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage. Mol. Cell. Biol. 31:4951–63
    [Google Scholar]
  255. 255.  Loveless TB, Topacio BR, Vashisht AA, Galaang S, Ulrich KM et al. 2015. DNA damage regulates translation through β-TRCP targeting of CReP. PLOS Genet 11:e1005292
    [Google Scholar]
  256. 256.  Brush MH, Shenolikar S 2008. Control of cellular GADD34 levels by the 26S proteasome. Mol. Cell. Biol. 28:6989–7000
    [Google Scholar]
  257. 257.  Liu X, Han W, Gulla S, Simon NI, Gao Y et al. 2016. Androgen ablation elicits PP1-dependence for AR stabilization and transactivation in prostate cancer. Prostate 76:649–61
    [Google Scholar]
  258. 258.  Opaluch AM, Schneider M, Chiang CY, Nguyen QT, Maestre AM et al. 2014. Positive regulation of TRAF6-dependent innate immune responses by protein phosphatase PP1-γ. PLOS ONE 9:e89284
    [Google Scholar]
  259. 259.  Xu J, Zhou JY, Xu Z, Kho DH, Zhuang Z et al. 2014. The role of Cullin3-mediated ubiquitination of the catalytic subunit of PP2A in TRAIL signaling. Cell Cycle 13:3750–58
    [Google Scholar]
  260. 260.  Hoffmeister M, Prelle C, Küchler P, Kovacevic I, Moser M et al. 2014. The ubiquitin E3 ligase NOSIP modulates protein phosphatase 2A activity in craniofacial development. PLOS ONE 9:e116150
    [Google Scholar]
  261. 261.  McDonald WJ, Thomas LN, Koirala S, Too CK 2014. Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac. Mol. Cell. Endocrinol. 382:254–61
    [Google Scholar]
  262. 262.  Du H, Wu K, Didoronkute A, Levy MV, Todi N et al. 2014. MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PLOS ONE 9:e107428
    [Google Scholar]
  263. 263.  Yabe R, Miura A, Usui T, Mudrak I, Ogris E et al. 2015. Protein phosphatase methyl-esterase PME-1 protects protein phosphatase 2A from ubiquitin/proteasome degradation. PLOS ONE 10:e0145226
    [Google Scholar]
  264. 264.  Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR et al. 2012. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit α4, altering PP2A stability and microtubule-associated protein phosphorylation. J. Biol. Chem. 287:24207–15
    [Google Scholar]
  265. 265.  Du H, Huang Y, Zaghlula M, Walters E, Cox TC, Massiah MA 2013. The MID1 E3 ligase catalyzes the polyubiquitination of Alpha4 (α4), a regulatory subunit of protein phosphatase 2A (PP2A): novel insights into MID1-mediated regulation of PP2A. J. Biol. Chem. 288:21341–50
    [Google Scholar]
  266. 266.  McDonald WJ, Sangster SM, Moffat LD, Henderson MJ, Too CK 2010. α4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)-binding protein. J. Cell. Biochem. 110:1123–29
    [Google Scholar]
  267. 267.  McConnell JL, Watkins GR, Soss SE, Franz HS, McCorvey LR et al. 2010. α4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry 49:1713–18
    [Google Scholar]
  268. 268.  Yu C, Ji SY, Sha QQ, Sun QY, Fan HY 2015. CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. Nat. Commun. 6:8017
    [Google Scholar]
  269. 269.  Oberg EA, Nifoussi SK, Gingras AC, Strack S 2012. Selective proteasomal degradation of the B′β subunit of protein phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15. J. Biol. Chem. 287:43378–89
    [Google Scholar]
  270. 270.  Wang X, Huang Y, Li L, Wei Q 2012. TRAF3 negatively regulates calcineurin-NFAT pathway by targeting calcineurin B subunit for degradation. IUBMB Life 64:748–56
    [Google Scholar]
  271. 271.  Kishi T, Ikeda A, Nagao R, Koyama N 2007. The SCFCdc4 ubiquitin ligase regulates calcineurin signaling through degradation of phosphorylated Rcn1, an inhibitor of calcineurin. PNAS 104:17418–23
    [Google Scholar]
  272. 272.  Hadweh P, Habelhah H, Kieff E, Mosialos G, Hatzivassiliou E 2014. The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation. Cell Signal 26:2730–37
    [Google Scholar]
  273. 273.  Dushukyan N, Dunn DM, Sager RA, Woodford MR, Loiselle DR et al. 2017. Phosphorylation and ubiquitination regulate protein phosphatase 5 activity and its prosurvival role in kidney cancer. Cell Rep 21:1883–95
    [Google Scholar]
  274. 274.  Sacco F, Perfetto L, Castagnoli L, Cesareni G 2012. The human phosphatase interactome: an intricate family portrait. FEBS Lett 586:2732–39
    [Google Scholar]
  275. 275.  Esseltine JL, Scott JD 2013. AKAP signaling complexes: pointing towards the next generation of therapeutic targets?. Trends Pharmacol. Sci. 34:648–55
    [Google Scholar]
  276. 276.  Woolfrey KM, Dell'Acqua ML 2015. Coordination of protein phosphorylation and dephosphorylation in synaptic plasticity. J. Biol. Chem. 290:28604–12
    [Google Scholar]
  277. 277.  Langeberg LK, Scott JD 2015. Signalling scaffolds and local organization of cellular behaviour. Nat. Rev. Mol. Cell Biol. 16:232–44
    [Google Scholar]
  278. 278.  Le AV, Tavalin SJ, Dodge-Kafka KL 2011. Identification of AKAP79 as a protein phosphatase 1 catalytic binding protein. Biochemistry 50:5279–91
    [Google Scholar]
  279. 279.  Blitzer RD, Connor JH, Brown GP, Wong T, Shenolikar S et al. 1998. Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. Science 280:1940–42
    [Google Scholar]
  280. 280.  Weber S, Meyer-Roxlau S, El-Armouche A 2016. Role of protein phosphatase inhibitor-1 in cardiac beta adrenergic pathway. J. Mol. Cell. Cardiol. 101:116–26
    [Google Scholar]
  281. 281.  Singh A, Redden JM, Kapiloff MS, Dodge-Kafka KL 2011. The large isoforms of A-kinase anchoring protein 18 mediate the phosphorylation of inhibitor-1 by protein kinase A and the inhibition of protein phosphatase 1 activity. Mol. Pharmacol. 79:533–40
    [Google Scholar]
  282. 282.  Hwang J, Pallas DC 2014. STRIPAK complexes: structure, biological function, and involvement in human diseases. Int. J. Biochem. Cell Biol. 47:118–48
    [Google Scholar]
  283. 283.  Shi Z, Jiao S, Zhou Z 2016. STRIPAK complexes in cell signaling and cancer. Oncogene 35:4549–57
    [Google Scholar]
  284. 284.  Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG et al. 2009. A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein. Mol. Cell Proteom. 8:157–71
    [Google Scholar]
  285. 285.  Gordon J, Hwang J, Carrier KJ, Jones CA, Kern QL et al. 2011. Protein phosphatase 2a (PP2A) binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3. BMC Biochem 12:54
    [Google Scholar]
  286. 286.  Andreazza S, Bouleau S, Martin B, Lamouroux A, Ponien P et al. 2015. Daytime CLOCK dephosphorylation is controlled by STRIPAK complexes in Drosophila. Cell Rep 11:1266–79
    [Google Scholar]
  287. 287.  Mulkey RM, Endo S, Shenolikar S, Malenka RC 1994. Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression. Nature 369:486–88
    [Google Scholar]
  288. 288.  Myers CT, Stong N, Mountier EI, Helbig KL, Freytag S et al. 2017. De novo mutations in PPP3CA cause severe neurodevelopmental disease with seizures. Am. J. Hum. Genet. 101:516–24
    [Google Scholar]
  289. 289.  Fernandez E, Schiappa R, Girault JA, Le Novère N 2006. DARPP-32 is a robust integrator of dopamine and glutamate signals. PLOS Comput. Biol. 2:e176
    [Google Scholar]
  290. 290.  Bollen M, Gerlich DW, Lesage B 2009. Mitotic phosphatases: from entry guards to exit guides. Trends Cell Biol 19:531–41
    [Google Scholar]
  291. 291.  De Wulf P, Montani F, Visintin R 2009. Protein phosphatases take the mitotic stage. Curr. Opin. Cell Biol. 21:806–15
    [Google Scholar]
  292. 292.  Wurzenberger C, Gerlich DW 2011. Phosphatases: providing safe passage through mitotic exit. Nat. Rev. Mol. Cell Biol. 12:469–82
    [Google Scholar]
  293. 293.  Qian J, Winkler C, Bollen M 2013. 4D-networking by mitotic phosphatases. Curr. Opin. Cell Biol. 25:697–703
    [Google Scholar]
  294. 294.  Rogers S, McCloy RA, Parker BL, Chaudhuri R, Gayevskiy V et al. 2015. Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells. Data Brief 5:45–52
    [Google Scholar]
  295. 295.  Kim HS, Fernades G, Lee CW 2016. Protein phosphatases involved in regulating mitosis: facts and hypotheses. Mol. Cells 39:654–62
    [Google Scholar]
  296. 296.  Heim A, Konietzny A, Mayer TU 2015. Protein phosphatase 1 is essential for Greatwall inactivation at mitotic exit. EMBO Rep 16:1501–10
    [Google Scholar]
  297. 297.  Wu JQ, Guo JY, Tang W, Yang CS, Freel CD et al. 2009. PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation. Nat. Cell Biol. 11:644–51
    [Google Scholar]
  298. 298.  Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R 2006. Phosphoproteome analysis of the human mitotic spindle. PNAS 103:5391–96
    [Google Scholar]
  299. 299.  Malik R, Nigg EA, Körner R 2008. Comparative conservation analysis of the human mitotic phosphoproteome. Bioinformatics 24:1426–32
    [Google Scholar]
  300. 300.  Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS et al. 2008. Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell 31:438–48
    [Google Scholar]
  301. 301.  Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML et al. 2010. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. 3:ra3
    [Google Scholar]
  302. 302.  Prévost M, Chamousset D, Nasa I, Freele E, Morrice N et al. 2013. Quantitative fragmentome mapping reveals novel, domain-specific partners for the modular protein RepoMan (recruits PP1 onto mitotic chromatin at anaphase). Mol. Cell Proteom. 12:1468–86
    [Google Scholar]
  303. 303.  Qian J, Beullens M, Huang J, De Munter S, Lesage B, Bollen M 2015. Cdk1 orders mitotic events through coordination of a chromosome-associated phosphatase switch. Nat. Commun. 6:10215
    [Google Scholar]
  304. 304.  Csermely P, Sandhu KS, Hazai E, Hoksza Z, Kiss HJM et al. 2012. Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review. Curr. Protein Pep. Sci. 13:19–33
    [Google Scholar]
  305. 305.  Mishra A, Oulès B, Pisco AO, Ly T, Liakath-Ali K et al. 2017. A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis. eLife 6:e27356
    [Google Scholar]
  306. 306.  Mochida S, Hunt T 2007. Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature 449:336–40
    [Google Scholar]
  307. 307.  Chircop M, Malladi CS, Lian AT, Page SL, Zavortink M et al. 2010. Calcineurin activity is required for the completion of cytokinesis. Cell Mol. Life Sci. 67:3725–37
    [Google Scholar]
  308. 308.  Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR 2015. Centromeric binding and activity of protein phosphatase 4. Nat. Commun. 206:5894
    [Google Scholar]
  309. 309.  Ollendorff V, Donoghue DJ 1997. The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex. J. Biol. Chem. 272:32011–18
    [Google Scholar]
  310. 310.  St-Denis N, Gupta GD, Lin ZY, Gonzalez-Badillo B, Veri AO et al. 2016. Phenotypic and interaction profiling of the human phosphatases identifies diverse mitotic regulators. Cell Rep 17:2488–501
    [Google Scholar]
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