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Protein Tyrosine Phosphatases: Structure, Function, and Implication in Human Disease

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Phosphatase Modulators

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1053))

Abstract

Protein tyrosine phosphorylation is a key regulatory mechanism in eukaryotic cell physiology. Aberrant expression or function of protein tyrosine kinases and protein tyrosine phosphatases can lead to serious human diseases, including cancer, diabetes, as well as cardiovascular, infectious, autoimmune, and neuropsychiatric disorders. Here, we give an overview of the protein tyrosine phosphatase superfamily with its over 100 members in humans. We review their structure, function, and implications in human diseases, and discuss their potential as novel drug targets, as well as current challenges and possible solutions to developing therapeutics based on these enzymes.

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References

  1. Hunter T (2000) Signaling—2000 and beyond. Cell 100:113–127

    Article  PubMed  CAS  Google Scholar 

  2. Pawson T, Scott JD (2005) Protein phosphorylation in signaling—50 years and counting. Trends Biochem Sci 30:286–290

    Article  PubMed  CAS  Google Scholar 

  3. Luan S (2003) Protein phosphatases in plants. Annu Rev Plant Biol 54:63–92

    Article  PubMed  CAS  Google Scholar 

  4. Deutscher J, Saier MHJ (2005) Ser/Thr/Tyr protein phosphorylation in bacteria—for long time neglected, now well established. J Mol Microbiol Biotechnol 9:125–131

    Article  PubMed  CAS  Google Scholar 

  5. Feher Z, Szirak K (1999) Signal transduction in fungi—the role of protein phosphorylation. Acta Microbiol Immunol Hung 46:269–271

    Article  PubMed  CAS  Google Scholar 

  6. Moorhead GB, De Wever V, Templeton G et al (2009) Evolution of protein phosphatases in plants and animals. Biochem J 417:401–409

    Article  PubMed  CAS  Google Scholar 

  7. Olsen JV, Blagoev B, Gnad F et al (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635–648

    Article  PubMed  CAS  Google Scholar 

  8. Hunter T, Sefton BM (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A 77:1311–1315

    Article  PubMed  CAS  Google Scholar 

  9. Hunter T (1998) The role of tyrosine phosphorylation in cell growth and disease. Harvey Lect 94:81–119

    PubMed  Google Scholar 

  10. Larsen M, Tremblay ML, Yamada KM (2003) Phosphatases in cell-matrix adhesion and migration. Nat Rev Mol Cell Biol 4:700–711

    Article  PubMed  CAS  Google Scholar 

  11. Alonso A, Sasin J, Bottini N et al (2004) Protein tyrosine phosphatases in the human genome. Cell 117:699–711

    Article  PubMed  CAS  Google Scholar 

  12. Mustelin T, Vang T, Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5:43–57

    Article  PubMed  CAS  Google Scholar 

  13. Tonks NK (2006) Protein tyrosine phosphatases: from genes, to function, to disease. Nat Rev Mol Cell Biol 7:833–846

    Article  PubMed  CAS  Google Scholar 

  14. Halle M, Tremblay ML, Meng TC (2007) Protein tyrosine phosphatases: emerging regulators of apoptosis. Cell Cycle 6:2773–2781

    Article  PubMed  CAS  Google Scholar 

  15. Pao LI, Badour K, Siminovitch KA et al (2007) Nonreceptor protein-tyrosine phosphatases in immune cell signaling. Annu Rev Immunol 25:473–523

    Article  PubMed  CAS  Google Scholar 

  16. Hunter T (2009) Tyrosine phosphorylation: thirty years and counting. Curr Opin Cell Biol 21:140–146

    Article  PubMed  CAS  Google Scholar 

  17. Rhee I, Veillette A (2012) Protein tyrosine phosphatases in lymphocyte activation and autoimmunity. Nat Immunol 13:439–447

    Article  PubMed  CAS  Google Scholar 

  18. Cohen P (2002) Protein kinases—the major drug targets of the twenty-first century? Nat Rev Drug Discov 1:309–315

    Article  PubMed  CAS  Google Scholar 

  19. Tautz L, Pellecchia M, Mustelin T (2006) Targeting the PTPome in human disease. Expert Opin Ther Targets 10:157–177

    Article  PubMed  CAS  Google Scholar 

  20. Andersen JN, Mortensen OH, Peters GH et al (2001) Structural and evolutionary relationships among protein tyrosine phosphatase domains. Mol Cell Biol 21:7117–7136

    Article  PubMed  CAS  Google Scholar 

  21. Pulido R, Hooft van Huijsduijnen R (2008) Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease. FEBS J 275:848–866

    Article  PubMed  CAS  Google Scholar 

  22. Patterson KI, Brummer T, O’Brien PM et al (2009) Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J 418:475–489

    PubMed  CAS  Google Scholar 

  23. Bottini N, Bottini E, Gloria-Bottini F et al (2002) Low-molecular-weight protein tyrosine phosphatase and human disease: in search of biochemical mechanisms. Arch Immunol Ther Exp (Warsz) 50:95–104

    CAS  Google Scholar 

  24. Zhang ZY, Wang Y, Dixon JE (1994) Dissecting the catalytic mechanism of protein-tyrosine phosphatases. Proc Natl Acad Sci U S A 91:1624–1627

    Article  PubMed  CAS  Google Scholar 

  25. Zhang ZY (1995) Kinetic and mechanistic characterization of a mammalian protein-tyrosine phosphatase, PTP1. J Biol Chem 270:11199–11204

    Article  PubMed  CAS  Google Scholar 

  26. Denu JM, Stuckey JA, Saper MA et al (1996) Form and function in protein dephosphorylation. Cell 87:361–364

    Article  PubMed  CAS  Google Scholar 

  27. Denu JM, Lohse DL, Vijayalakshmi J et al (1996) Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis. Proc Natl Acad Sci U S A 93:2493–2498

    Article  PubMed  CAS  Google Scholar 

  28. Stuckey JA, Schubert HL, Fauman EB et al (1994) Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 A and the complex with tungstate. Nature 370:571–575

    Article  PubMed  CAS  Google Scholar 

  29. Hengge AC, Denu JM, Dixon JE (1996) Transition-state structures for the native dual-specific phosphatase VHR and D92N and S131A mutants. Contributions to the driving force for catalysis. Biochemistry 35:7084–7092

    Article  PubMed  CAS  Google Scholar 

  30. Zhang ZY (2002) Protein tyrosine phosphatases, structure and function, substrate specificity, and inhibitor development. Annu Rev Pharmacol Toxicol 42:209–234

    Article  PubMed  CAS  Google Scholar 

  31. Zhang ZY, Maclean D, McNamara DJ et al (1994) Protein tyrosine phosphatase substrate specificity: size and phosphotyrosine positioning requirements in peptide substrates. Biochemistry 33:2285–2290

    Article  PubMed  CAS  Google Scholar 

  32. Mustelin T, Tautz L, Page R (2005) Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site. J Mol Biol 354:150–163

    Article  PubMed  CAS  Google Scholar 

  33. Barr AJ, Ugochukwu E, Lee WH et al (2009) Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell 136:352–363

    Article  PubMed  CAS  Google Scholar 

  34. Wiesmann C, Barr KJ, Kung J et al (2004) Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol 11:730–737

    Article  PubMed  CAS  Google Scholar 

  35. Kamerlin SC, Rucker R, Boresch S (2007) A molecular dynamics study of WPD-loop flexibility in PTP1B. Biochem Biophys Res Commun 356:1011–1016

    Article  PubMed  CAS  Google Scholar 

  36. Vang T, Liu WH, Delacroix L et al (2012) LYP inhibits T-cell activation when dissociated from CSK. Nat Chem Biol 8:437–446

    Article  PubMed  CAS  Google Scholar 

  37. Lorenz U (2009) SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunol Rev 228:342–359

    Article  PubMed  Google Scholar 

  38. Pei D, Lorenz U, Klingmuller U et al (1994) Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. Biochemistry 33:15483–15493

    Article  PubMed  CAS  Google Scholar 

  39. Hof P, Pluskey S, Dhe-Paganon S et al (1998) Crystal structure of the tyrosine phosphatase SHP-2. Cell 92:441–450

    Article  PubMed  CAS  Google Scholar 

  40. Johnson P, Ostergaard HL, Wasden C et al (1992) Mutational analysis of CD45. A leukocyte-specific protein tyrosine phosphatase. J Biol Chem 267:8035–8041

    PubMed  CAS  Google Scholar 

  41. Streuli M, Krueger NX, Thai T et al (1990) Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. EMBO J 9:2399–2407

    PubMed  CAS  Google Scholar 

  42. Kashio N, Matsumoto W, Parker S et al (1998) The second domain of the CD45 protein tyrosine phosphatase is critical for interleukin-2 secretion and substrate recruitment of TCR-zeta in vivo. J Biol Chem 273:33856–33863

    Article  PubMed  CAS  Google Scholar 

  43. Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139:468–484

    Article  PubMed  CAS  Google Scholar 

  44. Barford D, Flint AJ, Tonks NK (1994) Crystal structure of human protein tyrosine phosphatase 1B. Science 263:1397–1404

    Article  PubMed  CAS  Google Scholar 

  45. Zhang ZY, Dixon JE (1993) Active site labeling of the Yersinia protein tyrosine phosphatase: the determination of the pKa of the active site cysteine and the function of the conserved histidine 402. Biochemistry 32:9340–9345

    Article  PubMed  CAS  Google Scholar 

  46. Tonks NK (2005) Redox redux: revisiting PTPs and the control of cell signaling. Cell 121:667–670

    Article  PubMed  CAS  Google Scholar 

  47. Chen YY, Chu HM, Pan KT et al (2008) Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation. J Biol Chem 283:35265–35272

    Article  PubMed  CAS  Google Scholar 

  48. Krishnan N, Fu C, Pappin DJ et al (2011) H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal 4:ra86

    Article  PubMed  CAS  Google Scholar 

  49. Keng YF, Wu L, Zhang ZY (1999) Probing the function of the conserved tryptophan in the flexible loop of the Yersinia protein-tyrosine phosphatase. Eur J Biochem 259:809–814

    Article  PubMed  CAS  Google Scholar 

  50. Hoff RH, Hengge AC, Wu L et al (2000) Effects on general acid catalysis from mutations of the invariant tryptophan and arginine residues in the protein tyrosine phosphatase from Yersinia. Biochemistry 39:46–54

    Article  PubMed  CAS  Google Scholar 

  51. Kurkcuoglu Z, Bakan A, Kocaman D et al (2012) Coupling between catalytic loop motions and enzyme global dynamics. PLoS Comput Biol 8:e1002705

    Article  PubMed  CAS  Google Scholar 

  52. Cui L, Yu WP, DeAizpurua HJ et al (1996) Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in insulin-dependent diabetes. J Biol Chem 271:24817–24823

    Article  PubMed  CAS  Google Scholar 

  53. Seifert RA, Coats SA, Oganesian A et al (2003) PTPRQ is a novel phosphatidylinositol phosphatase that can be expressed as a cytoplasmic protein or as a subcellularly localized receptor-like protein. Exp Cell Res 287:374–386

    Article  PubMed  CAS  Google Scholar 

  54. Cheng J, Wu K, Armanini M et al (1997) A novel protein-tyrosine phosphatase related to the homotypically adhering kappa and mu receptors. J Biol Chem 272:7264–7277

    Article  PubMed  CAS  Google Scholar 

  55. Gingras MC, Zhang YL, Kharitidi D et al (2009) HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS One 4:e5105

    Article  PubMed  CAS  Google Scholar 

  56. Cardone L, Carlucci A, Affaitati A et al (2004) Mitochondrial AKAP121 binds and targets protein tyrosine phosphatase D1, a novel positive regulator of src signaling. Mol Cell Biol 24:4613–4626

    Article  PubMed  CAS  Google Scholar 

  57. Rabin DU, Pleasic SM, Shapiro JA et al (1994) Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. J Immunol 152:3183–3188

    PubMed  CAS  Google Scholar 

  58. Jia Z, Barford D, Flint AJ et al (1995) Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B. Science 268:1754–1758

    Article  PubMed  CAS  Google Scholar 

  59. Eswaran J, von Kries JP, Marsden B et al (2006) Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases. Biochem J 395:483–491

    Article  PubMed  CAS  Google Scholar 

  60. Iversen LF, Moller KB, Pedersen AK et al (2002) Structure determination of T cell protein-tyrosine phosphatase. J Biol Chem 277:19982–19990

    Article  PubMed  CAS  Google Scholar 

  61. Yang J, Cheng Z, Niu T et al (2000) Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1. J Biol Chem 275:4066–4071

    Article  PubMed  CAS  Google Scholar 

  62. Asante-Appiah E, Patel S, Desponts C et al (2006) Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits inhibitor selectivity over T-cell protein-tyrosine phosphatase. J Biol Chem 281:8010–8015

    Article  PubMed  CAS  Google Scholar 

  63. Critton DA, Tautz L, Page R (2011) Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD loop involves coordinated movement of the E loop. J Mol Biol 405:619–629

    Article  PubMed  CAS  Google Scholar 

  64. Xie L, Zhang YL, Zhang ZY (2002) Design and characterization of an improved protein tyrosine phosphatase substrate-trapping mutant. Biochemistry 41:4032–4039

    Article  PubMed  CAS  Google Scholar 

  65. Zhao Y, Wu L, Noh SJ et al (1998) Altering the nucleophile specificity of a protein-tyrosine phosphatase-catalyzed reaction. Probing the function of the invariant glutamine residues. J Biol Chem 273:5484–5492

    Article  PubMed  CAS  Google Scholar 

  66. Pedersen AK, Guo XL, Moller KB et al (2004) Residue 182 influences the second step of protein-tyrosine phosphatase-mediated catalysis. Biochem J 378:421–433

    Article  PubMed  CAS  Google Scholar 

  67. Zabell AP, Schroff ADJ, Bain BE et al (2006) Crystal structure of the human B-form low molecular weight phosphotyrosyl phosphatase at 1.6-A resolution. J Biol Chem 281:6520–6527

    Article  PubMed  CAS  Google Scholar 

  68. Bryson GL, Massa H, Trask BJ et al (1995) Gene structure, sequence, and chromosomal localization of the human red cell-type low-molecular-weight acid phosphotyrosyl phosphatase gene, ACP1. Genomics 30:133–140

    Article  PubMed  CAS  Google Scholar 

  69. Tailor P, Gilman J, Williams S et al (1999) A novel isoform of the low molecular weight phosphotyrosine phosphatase, LMPTP-C, arising from alternative mRNA splicing. Eur J Biochem 262:277–282

    Article  PubMed  CAS  Google Scholar 

  70. Ramponi G, Manao G, Camici G et al (1989) The 18 kDa cytosolic acid phosphatase from bovine live has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor. FEBS Lett 250:469–473

    Article  PubMed  CAS  Google Scholar 

  71. Rudolph J (2007) Cdc25 phosphatases: structure, specificity, and mechanism. Biochemistry 46:3595–3604

    Article  PubMed  CAS  Google Scholar 

  72. Mailand N, Falck J, Lukas C et al (2000) Rapid destruction of human Cdc25A in response to DNA damage. Science 288:1425–1429

    Article  PubMed  CAS  Google Scholar 

  73. Donzelli M, Squatrito M, Ganoth D et al (2002) Dual mode of degradation of Cdc25 A phosphatase. EMBO J 21:4875–4884

    Article  PubMed  CAS  Google Scholar 

  74. Conklin DS, Galaktionov K, Beach D (1995) 14-3-3 proteins associate with cdc25 phosphatases. Proc Natl Acad Sci U S A 92:7892–7896

    Article  PubMed  CAS  Google Scholar 

  75. Forrest A, Gabrielli B (2001) Cdc25B activity is regulated by 14-3-3. Oncogene 20:4393–4401

    Article  PubMed  CAS  Google Scholar 

  76. Giles N, Forrest A, Gabrielli B (2003) 14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity. J Biol Chem 278:28580–28587

    Article  PubMed  CAS  Google Scholar 

  77. Hoffmann I, Clarke PR, Marcote MJ et al (1993) Phosphorylation and activation of human cdc25-C by cdc2–cyclin B and its involvement in the self-amplification of MPF at mitosis. EMBO J 12:53–63

    PubMed  CAS  Google Scholar 

  78. Hoffmann I, Draetta G, Karsenti E (1994) Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J 13:4302–4310

    PubMed  CAS  Google Scholar 

  79. Fauman EB, Cogswell JP, Lovejoy B et al (1998) Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell 93:617–625

    Article  PubMed  CAS  Google Scholar 

  80. Reynolds RA, Yem AW, Wolfe CL et al (1999) Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol 293:559–568

    Article  PubMed  CAS  Google Scholar 

  81. Hofmann K, Bucher P, Kajava AV (1998) A model of Cdc25 phosphatase catalytic domain and Cdk-interaction surface based on the presence of a rhodanese homology domain. J Mol Biol 282:195–208

    Article  PubMed  CAS  Google Scholar 

  82. Sarmiento M, Zhao Y, Gordon SJ et al (1998) Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B. J Biol Chem 273:26368–26374

    Article  PubMed  CAS  Google Scholar 

  83. Huang Z, Zhou B, Zhang ZY (2004) Molecular determinants of substrate recognition in hematopoietic protein-tyrosine phosphatase. J Biol Chem 279:52150–52159

    Article  PubMed  CAS  Google Scholar 

  84. Francis DM, Rozycki B, Tortajada A et al (2011) Resting and Active States of the ERK2:HePTP Complex. J Am Chem Soc 133:17138–17141

    Article  PubMed  CAS  Google Scholar 

  85. Francis DM, Rozycki B, Koveal D et al (2011) structural basis of p38a regulation by hematopoietic tyrosine phosphatase. Nat Chem Biol 7:916–924

    Article  PubMed  CAS  Google Scholar 

  86. Wiland AM, Denu JM, Mourey RJ et al (1996) Purification and kinetic characterization of the mitogen-activated protein kinase phosphatase rVH6. J Biol Chem 271:33486–33492

    Article  PubMed  CAS  Google Scholar 

  87. Zhao Y, Zhang ZY (2001) The mechanism of dephosphorylation of extracellular signal-regulated kinase 2 by mitogen-activated protein kinase phosphatase 3. J Biol Chem 276:32382–32391

    Article  PubMed  CAS  Google Scholar 

  88. Begley MJ, Taylor GS, Kim SA et al (2003) Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell 12:1391–1402

    Article  PubMed  CAS  Google Scholar 

  89. Puius YA, Zhao Y, Sullivan M et al (1997) Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design. Proc Natl Acad Sci U S A 94:13420–13425

    Article  PubMed  CAS  Google Scholar 

  90. Salmeen A, Andersen JN, Myers MP et al (2000) Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell 6:1401–1412

    Article  PubMed  CAS  Google Scholar 

  91. Peters GH, Iversen LF, Branner S et al (2000) Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha. J Biol Chem 275:18201–18209

    Article  PubMed  CAS  Google Scholar 

  92. Flint AJ, Tiganis T, Barford D et al (1997) Development of “substrate-trapping” mutants to identify physiological substrates of protein tyrosine phosphatases. Proc Natl Acad Sci U S A 94:1680–1685

    Article  PubMed  CAS  Google Scholar 

  93. Sarmiento M, Puius YA, Vetter SW et al (2000) Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition. Biochemistry 39:8171–8179

    Article  PubMed  CAS  Google Scholar 

  94. Song H, Hanlon N, Brown NR et al (2001) Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell 7:615–626

    Article  PubMed  CAS  Google Scholar 

  95. Wang S, Tabernero L, Zhang M et al (2000) Crystal structures of a low-molecular weight protein tyrosine phosphatase from Saccharomyces cerevisiae and its complex with the substrate p-nitrophenyl phosphate. Biochemistry 39:1903–1914

    Article  PubMed  CAS  Google Scholar 

  96. Garton AJ, Flint AJ, Tonks NK (1996) Identification of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. Mol Cell Biol 16:6408–6418

    PubMed  CAS  Google Scholar 

  97. Blanchetot C, Chagnon M, Dube N et al (2005) Substrate-trapping techniques in the identification of cellular PTP targets. Methods 35:44–53

    Article  PubMed  CAS  Google Scholar 

  98. Agazie YM, Hayman MJ (2003) Development of an efficient “substrate-trapping” mutant of Src homology phosphotyrosine phosphatase 2 and identification of the epidermal growth factor receptor, Gab1, and three other proteins as target substrates. J Biol Chem 278:13952–13958

    Article  PubMed  CAS  Google Scholar 

  99. Sohn J, Parks JM, Buhrman G et al (2005) Experimental validation of the docking orientation of Cdc25 with its Cdk2-CycA protein substrate. Biochemistry 44:16563–16573

    Article  CAS  PubMed  Google Scholar 

  100. Buhrman G, Parker B, Sohn J et al (2005) Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond. Biochemistry 44:5307–5316

    Article  CAS  PubMed  Google Scholar 

  101. Ostman A, Hellberg C, Bohmer FD (2006) Protein-tyrosine phosphatases and cancer. Nat Rev Cancer 6:307–320

    Article  PubMed  CAS  Google Scholar 

  102. Vang T, Miletic AV, Arimura Y et al (2008) Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol 26:29–55

    Article  PubMed  CAS  Google Scholar 

  103. Julien SG, Dube N, Hardy S et al (2011) Inside the human cancer tyrosine phosphatome. Nat Rev Cancer 11:35–49

    Article  CAS  PubMed  Google Scholar 

  104. Goebel-Goody SM, Baum M, Paspalas CD et al (2012) Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders. Pharmacol Rev 64:65–87

    Article  PubMed  CAS  Google Scholar 

  105. Keniry M, Parsons R (2008) The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 27:5477–5485

    Article  PubMed  CAS  Google Scholar 

  106. Mena-Duran AV, Togo SH, Bazhenova L et al (2005) SHP1 expression in bone marrow biopsies of myelodysplastic syndrome patients: a new prognostic factor. Br J Haematol 129:791–794

    Article  PubMed  CAS  Google Scholar 

  107. Zhang Q, Wang HY, Marzec M et al (2005) STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes. Proc Natl Acad Sci U S A 102:6948–6953

    Article  PubMed  CAS  Google Scholar 

  108. Mohi MG, Neel BG (2007) The role of Shp2 (PTPN11) in cancer. Curr Opin Genet Dev 17:23–30

    Article  PubMed  CAS  Google Scholar 

  109. Xu R (2007) Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia. Cell Res 17:295–297

    Article  PubMed  CAS  Google Scholar 

  110. Saha S, Bardelli A, Buckhaults P et al (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294:1343–1346

    Article  PubMed  CAS  Google Scholar 

  111. Loda M, Capodieci P, Mishra R et al (1996) Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis. Am J Pathol 149:1553–1564

    PubMed  CAS  Google Scholar 

  112. Jiang ZX, Zhang ZY (2008) Targeting PTPs with small molecule inhibitors in cancer treatment. Cancer Metastasis Rev 27:263–272

    Article  PubMed  CAS  Google Scholar 

  113. Bourdeau A, Dube N, Tremblay ML (2005) Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP. Curr Opin Cell Biol 17:203–209

    Article  PubMed  CAS  Google Scholar 

  114. Julien SG, Dube N, Read M et al (2007) Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat Genet 39:338–346

    Article  PubMed  CAS  Google Scholar 

  115. Bentires-Alj M, Neel BG (2007) Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res 67:2420–2424

    Article  PubMed  CAS  Google Scholar 

  116. Tonks NK, Muthuswamy SK (2007) A brake becomes an accelerator: PTP1B—a new therapeutic target for breast cancer. Cancer Cell 11:214–216

    Article  PubMed  CAS  Google Scholar 

  117. Bottini N, Musumeci L, Alonso A et al (2004) A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 36:337–338

    Article  PubMed  CAS  Google Scholar 

  118. Begovich AB, Carlton VE, Honigberg LA et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75:330–337

    Article  PubMed  CAS  Google Scholar 

  119. Kyogoku C, Langefeld CD, Ortmann WA et al (2004) Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 75:504–507

    Article  PubMed  CAS  Google Scholar 

  120. Stanford SM, Mustelin TM, Bottini N (2010) Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases. Semin Immunopathol 32:127–136

    Article  PubMed  CAS  Google Scholar 

  121. Negro R, Gobessi S, Longo PG et al (2012) Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT. Blood 119:6278–6287

    Article  PubMed  CAS  Google Scholar 

  122. Saxena M, Williams S, Brockdorff J et al (1999) Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP). J Biol Chem 274:11693–11700

    Article  PubMed  CAS  Google Scholar 

  123. Zanke B, Squire J, Griesser H et al (1994) A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1. Leukemia 8:236–244

    PubMed  CAS  Google Scholar 

  124. Sergienko E, Xu J, Liu WH et al (2012) Inhibition of hematopoietic protein tyrosine phosphatase augments and prolongs ERK1/2 and p38 activation. ACS Chem Biol 7:367–377

    Article  PubMed  CAS  Google Scholar 

  125. Fonatsch C, Haase D, Freund M et al (1991) Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes? Cancer Genet Cytogenet 56:243–253

    Article  PubMed  CAS  Google Scholar 

  126. Mamaev N, Mamaeva SE, Pavlova VA et al (1988) Combined trisomy 1q and monosomy 17p due to translocation t(1;17) in a patient with myelodysplastic syndrome. Cancer Genet Cytogenet 35:21–25

    Article  PubMed  CAS  Google Scholar 

  127. Souza AC, Azoubel S, Queiroz KC et al (2009) From immune response to cancer: a spot on the low molecular weight protein tyrosine phosphatase. Cell Mol Life Sci 66:1140–1153

    Article  PubMed  CAS  Google Scholar 

  128. Minassian BA, Lee JR, Herbrick JA et al (1998) Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Nat Genet 20:171–174

    Article  PubMed  CAS  Google Scholar 

  129. Laporte J, Hu LJ, Kretz C et al (1996) A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet 13:175–182

    Article  PubMed  CAS  Google Scholar 

  130. Bolino A, Muglia M, Conforti FL et al (2000) Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet 25:17–19

    Article  PubMed  CAS  Google Scholar 

  131. Azzedine H, Bolino A, Taieb T et al (2003) Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. Am J Hum Genet 72:1141–1153

    Article  PubMed  CAS  Google Scholar 

  132. Kung C, Pingel JT, Heikinheimo M et al (2000) Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med 6:343–345

    Article  PubMed  CAS  Google Scholar 

  133. Elchebly M, Payette P, Michaliszyn E et al (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548

    Article  PubMed  CAS  Google Scholar 

  134. Zhang S, Zhang ZY (2007) PTP1B as a drug target: recent developments in PTP1B inhibitor discovery. Drug Discov Today 12:373–381

    Article  PubMed  CAS  Google Scholar 

  135. Lee S, Wang Q (2007) Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B. Med Res Rev 27:553–573

    Article  PubMed  CAS  Google Scholar 

  136. Barr AJ (2010) Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development. Future Med Chem 2:1563–1576

    Article  PubMed  CAS  Google Scholar 

  137. Popov D (2011) Novel protein tyrosine phosphatase 1B inhibitors: interaction requirements for improved intracellular efficacy in type 2 diabetes mellitus and obesity control. Biochem Biophys Res Commun 410:377–381

    Article  PubMed  CAS  Google Scholar 

  138. Siegel PM, Ryan ED, Cardiff RD et al (1999) Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J 18:2149–2164

    Article  PubMed  CAS  Google Scholar 

  139. Tanner MM, Grenman S, Koul A et al (2000) Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res 6:1833–1839

    PubMed  CAS  Google Scholar 

  140. Ginestier C, Cervera N, Finetti P et al (2006) Prognosis and gene expression profiling of 20q13-amplified breast cancers. Clin Cancer Res 12:4533–4544

    Article  PubMed  CAS  Google Scholar 

  141. Wiener JR, Kerns BJ, Harvey EL et al (1994) Overexpression of the protein tyrosine phosphatase PTP1B in human breast cancer: association with p185c-erbB-2 protein expression. J Natl Cancer Inst 86:372–378

    Article  PubMed  CAS  Google Scholar 

  142. Zhai YF, Beittenmiller H, Wang B et al (1993) Increased expression of specific protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene. Cancer Res 53:2272–2278

    PubMed  CAS  Google Scholar 

  143. Bjorge JD, Pang A, Fujita DJ (2000) Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines. J Biol Chem 275:41439–41446

    Article  PubMed  CAS  Google Scholar 

  144. Arias-Romero LE, Saha S, Villamar-Cruz O et al (2009) Activation of Src by protein tyrosine phosphatase 1B Is required for ErbB2 transformation of human breast epithelial cells. Cancer Res 69:4582–4588

    Article  PubMed  CAS  Google Scholar 

  145. Kaminski R, Zagozdzon R, Fu Y et al (2006) Role of SRC kinases in Neu-induced tumorigenesis: challenging the paradigm using Csk homologous kinase transgenic mice. Cancer Res 66:5757–5762

    Article  PubMed  CAS  Google Scholar 

  146. Dadke S, Chernoff J (2003) Protein-tyrosine phosphatase 1B mediates the effects of insulin on the actin cytoskeleton in immortalized fibroblasts. J Biol Chem 278:40607–40611

    Article  PubMed  CAS  Google Scholar 

  147. Dube N, Cheng A, Tremblay ML (2004) The role of protein tyrosine phosphatase 1B in Ras signaling. Proc Natl Acad Sci U S A 101:1834–1839

    Article  PubMed  CAS  Google Scholar 

  148. Kashige N, Carpino N, Kobayashi R (2000) Tyrosine phosphorylation of p62dok by p210bcr-abl inhibits RasGAP activity. Proc Natl Acad Sci U S A 97:2093–2098

    Article  PubMed  CAS  Google Scholar 

  149. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  PubMed  CAS  Google Scholar 

  150. Bange J, Zwick E, Ullrich A (2001) Molecular targets for breast cancer therapy and prevention. Nat Med 7:548–552

    Article  PubMed  CAS  Google Scholar 

  151. Carter P, Presta L, Gorman CM et al (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 89:4285–4289

    Article  PubMed  CAS  Google Scholar 

  152. Nahta R, Esteva FJ (2007) Trastuzumab: triumphs and tribulations. Oncogene 26:3637–3643

    Article  PubMed  CAS  Google Scholar 

  153. Grossmann KS, Rosario M, Birchmeier C et al (2010) The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res 106:53–89

    Article  PubMed  CAS  Google Scholar 

  154. Liu X, Qu CK (2011) Protein tyrosine phosphatase SHP-2 (PTPN11) in hematopoiesis and leukemogenesis. J Signal Transduct 2011:195–239

    Google Scholar 

  155. Tartaglia M, Mehler EL, Goldberg R et al (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29:465–468

    Article  PubMed  CAS  Google Scholar 

  156. Noonan JA (1968) Hypertelorism with turner phenotype. a new syndrome with associated congenital heart disease. Am J Dis Child 116:373–380

    PubMed  CAS  Google Scholar 

  157. Allanson JE (1987) Noonan syndrome. J Med Genet 24:9–13

    Article  PubMed  CAS  Google Scholar 

  158. Marino B, Digilio MC, Toscano A et al (1999) Congenital heart diseases in children with Noonan syndrome: an expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr 135:703–706

    Article  PubMed  CAS  Google Scholar 

  159. Opitz JM (1985) The Noonan syndrome. Am J Med Genet 21:515–518

    Article  PubMed  CAS  Google Scholar 

  160. Tartaglia M, Gelb BD (2005) Noonan syndrome and related disorders: genetics and pathogenesis. Annu Rev Genomics Hum Genet 6:45–68

    Article  PubMed  CAS  Google Scholar 

  161. Tartaglia M, Niemeyer CM, Fragale A et al (2003) Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 34:148–150

    Article  PubMed  CAS  Google Scholar 

  162. Bentires-Alj M, Paez JG, David FS et al (2004) Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res 64:8816–8820

    Article  PubMed  CAS  Google Scholar 

  163. Chan RJ, Feng GS (2007) PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase. Blood 109:862–867

    Article  PubMed  CAS  Google Scholar 

  164. Chan G, Kalaitzidis D, Neel BG (2008) The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev 27:179–192

    Article  PubMed  CAS  Google Scholar 

  165. Barford D, Neel BG (1998) Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure 6:249–254

    Article  PubMed  CAS  Google Scholar 

  166. Araki T, Mohi MG, Ismat FA et al (2004) Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med 10:849–857

    Article  PubMed  CAS  Google Scholar 

  167. Chan RJ, Leedy MB, Munugalavadla V et al (2005) Human somatic PTPN11 mutations induce hematopoietic-cell hypersensitivity to granulocyte-macrophage colony-stimulating factor. Blood 105:3737–3742

    Article  PubMed  CAS  Google Scholar 

  168. Fragale A, Tartaglia M, Wu J et al (2004) Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation. Hum Mutat 23:267–277

    Article  PubMed  CAS  Google Scholar 

  169. Krenz M, Gulick J, Osinska HE et al (2008) Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A 105:18930–18935

    Article  PubMed  CAS  Google Scholar 

  170. Mohi MG, Williams IR, Dearolf CR et al (2005) Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations. Cancer Cell 7:179–191

    Article  PubMed  CAS  Google Scholar 

  171. Yu WM, Daino H, Chen J et al (2006) Effects of a leukemia-associated gain-of-function mutation of SHP-2 phosphatase on interleukin-3 signaling. J Biol Chem 281:5426–5434

    Article  PubMed  CAS  Google Scholar 

  172. Carta C, Pantaleoni F, Bocchinfuso G et al (2006) Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet 79:129–135

    Article  PubMed  CAS  Google Scholar 

  173. Schubbert S, Zenker M, Rowe SL et al (2006) Germline KRAS mutations cause Noonan syndrome. Nat Genet 38:331–336

    Article  PubMed  CAS  Google Scholar 

  174. Roberts AE, Araki T, Swanson KD et al (2007) Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet 39:70–74

    Article  PubMed  CAS  Google Scholar 

  175. Tartaglia M, Pennacchio LA, Zhao C et al (2007) Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet 39:75–79

    Article  PubMed  CAS  Google Scholar 

  176. Tartaglia M, Martinelli S, Cazzaniga G et al (2004) Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood 104:307–313

    Article  PubMed  CAS  Google Scholar 

  177. Shi ZQ, Yu DH, Park M et al (2000) Molecular mechanism for the Shp-2 tyrosine phosphatase function in promoting growth factor stimulation of Erk activity. Mol Cell Biol 20:1526–1536

    Article  PubMed  CAS  Google Scholar 

  178. Nguyen TV, Ke Y, Zhang EE et al (2006) Conditional deletion of Shp2 tyrosine phosphatase in thymocytes suppresses both pre-TCR and TCR signals. J Immunol 177:5990–5996

    PubMed  CAS  Google Scholar 

  179. Matozaki T, Murata Y, Saito Y et al (2009) Protein tyrosine phosphatase SHP-2: a proto-oncogene product that promotes Ras activation. Cancer Sci 100:1786–1793

    Article  PubMed  CAS  Google Scholar 

  180. Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28:284–293

    Article  PubMed  CAS  Google Scholar 

  181. Loh ML (2011) Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol 152:677–687

    Article  PubMed  CAS  Google Scholar 

  182. Le DT, Kong N, Zhu Y et al (2004) Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder. Blood 103:4243–4250

    Article  PubMed  CAS  Google Scholar 

  183. Chen L, Sung SS, Yip ML et al (2006) Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol 70:562–570

    Article  PubMed  CAS  Google Scholar 

  184. Noren-Muller A, Reis-Correa IJ, Prinz H et al (2006) Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis. Proc Natl Acad Sci U S A 103:10606–10611

    Article  PubMed  CAS  Google Scholar 

  185. Hellmuth K, Grosskopf S, Lum CT et al (2008) Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking. Proc Natl Acad Sci U S A 105:7275–7280

    Article  PubMed  CAS  Google Scholar 

  186. Lawrence HR, Pireddu R, Chen L et al (2008) Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem 51:4948–4956

    Article  PubMed  CAS  Google Scholar 

  187. Zhang X, He Y, Liu S et al (2010) Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). J Med Chem 53:2482–2493

    Article  PubMed  CAS  Google Scholar 

  188. Liu S, Yu Z, Yu X et al (2011) SHP2 is a target of the immunosuppressant tautomycetin. Chem Biol 18:101–110

    Article  PubMed  CAS  Google Scholar 

  189. Baum ML, Kurup P, Xu J et al (2010) A STEP forward in neural function and degeneration. Commun Integr Biol 3:419–422

    Article  PubMed  CAS  Google Scholar 

  190. Zhang Y, Kurup P, Xu J et al (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107:19014–19019

    Article  PubMed  CAS  Google Scholar 

  191. Snyder EM, Nong Y, Almeida CG et al (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 8:1051–1058

    Article  PubMed  CAS  Google Scholar 

  192. Chin J, Palop JJ, Puolivali J et al (2005) Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci 25:9694–9703

    Article  PubMed  CAS  Google Scholar 

  193. Zhang Y, Venkitaramani DV, Gladding CM et al (2008) The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation. J Neurosci 28:10561–10566

    Article  PubMed  CAS  Google Scholar 

  194. Zhang Y, Kurup P, Xu J et al (2011) Reduced levels of the tyrosine phosphatase STEP block beta amyloid-mediated GluA1/GluA2 receptor internalization. J Neurochem 119:664–672

    Article  PubMed  CAS  Google Scholar 

  195. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185

    Article  PubMed  CAS  Google Scholar 

  196. Selkoe DJ (1991) The molecular pathology of Alzheimer’s disease. Neuron 6:487–498

    Article  PubMed  CAS  Google Scholar 

  197. Kurup P, Zhang Y, Xu J et al (2010) Abeta-mediated NMDA receptor endocytosis in Alzheimer’s disease involves ubiquitination of the tyrosine phosphatase STEP61. J Neurosci 30:5948–5957

    Article  PubMed  CAS  Google Scholar 

  198. Bialy L, Waldmann H (2005) Inhibitors of protein tyrosine phosphatases: next-generation drugs? Angew Chem Int Ed Engl 44:3814–3839

    Article  PubMed  CAS  Google Scholar 

  199. Vintonyak VV, Antonchick AP, Rauh D et al (2009) The therapeutic potential of phosphatase inhibitors. Curr Opin Chem Biol 13:272–283

    Article  PubMed  CAS  Google Scholar 

  200. Sobhia ME, Paul S, Shinde R et al (2012) Protein tyrosine phosphatase inhibitors: a patent review (2002–2011). Expert Opin Ther Pat 22:125–153

    Article  PubMed  CAS  Google Scholar 

  201. He R, Zeng LF, He Y et al (2012) Small molecule tools for functional interrogation of protein tyrosine phosphatases. FEBS J 280:731–750

    Article  PubMed  CAS  Google Scholar 

  202. Burke TRJ, Kole HK, Roller PP (1994) Potent inhibition of insulin receptor dephosphorylation by a hexamer peptide containing the phosphotyrosyl mimetic F2Pmp. Biochem Biophys Res Commun 204:129–134

    Article  PubMed  CAS  Google Scholar 

  203. Lipinski CA, Lombardo F, Dominy BW et al (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26

    Article  PubMed  CAS  Google Scholar 

  204. Andersen HS, Olsen OH, Iversen LF et al (2002) Discovery and SAR of a novel selective and orally bioavailable nonpeptide classical competitive inhibitor class of protein-tyrosine phosphatase 1B. J Med Chem 45:4443–4459

    Article  PubMed  CAS  Google Scholar 

  205. Erbe DV, Klaman LD, Wilson DP et al (2009) Prodrug delivery of novel PTP1B inhibitors to enhance insulin signalling. Diabetes Obes Metab 11:579–588

    Article  PubMed  CAS  Google Scholar 

  206. Yu X, Sun JP, He Y et al (2007) Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A 104:19767–19772

    Article  PubMed  CAS  Google Scholar 

  207. Liu S, Zeng LF, Wu L et al (2008) Targeting inactive enzyme conformation: aryl diketoacid derivatives as a new class of PTP1B inhibitors. J Am Chem Soc 130:17075–17084

    Article  PubMed  CAS  Google Scholar 

  208. Wu S, Bottini M, Rickert RC et al (2009) In silico screening for PTPN22 inhibitors: active hits from an inactive phosphatase conformation. ChemMedChem 4:440–444

    Article  PubMed  CAS  Google Scholar 

  209. Zhang XY, Bishop AC (2007) Site-specific incorporation of allosteric-inhibition sites in a protein tyrosine phosphatase. J Am Chem Soc 129:3812–3813

    Article  PubMed  CAS  Google Scholar 

  210. Tautz L, Mustelin T (2007) Strategies for developing protein tyrosine phosphatase inhibitors. Methods 42:250–260

    Article  PubMed  CAS  Google Scholar 

  211. Pot DA, Dixon JE (1992) Active site labeling of a receptor-like protein tyrosine phosphatase. J Biol Chem 267:140–143

    PubMed  CAS  Google Scholar 

  212. Zhang ZY, Davis JP, Van Etten RL (1992) Covalent modification and active site-directed inactivation of a low molecular weight phosphotyrosyl protein phosphatase. Biochemistry 31:1701–1711

    Article  PubMed  CAS  Google Scholar 

  213. Liu S, Zhou B, Yang H et al (2008) Aryl vinyl sulfonates and sulfones as active site-directed and mechanism-based probes for protein tyrosine phosphatases. J Am Chem Soc 130:8251–8260

    Article  PubMed  CAS  Google Scholar 

  214. Kim JH, Cho H, Ryu SE et al (2000) Effects of metal ions on the activity of protein tyrosine phosphatase VHR: highly potent and reversible oxidative inactivation by Cu2+ ion. Arch Biochem Biophys 382:72–80

    Article  PubMed  CAS  Google Scholar 

  215. Niesen FH, Berglund H, Vedadi M (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2:2212–2221

    Article  PubMed  CAS  Google Scholar 

  216. Rhee SG, Chang TS, Bae YS et al (2003) Cellular regulation by hydrogen peroxide. J Am Soc Nephrol 14:S211–S215

    Article  PubMed  CAS  Google Scholar 

  217. Miki H, Funato Y (2012) Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species. J Biochem 151:255–261

    Article  PubMed  CAS  Google Scholar 

  218. Roos G, Messens J (2011) Protein sulfenic acid formation: from cellular damage to redox regulation. Free Radic Biol Med 51:314–326

    Article  PubMed  CAS  Google Scholar 

  219. Poole LB, Karplus PA, Claiborne A (2004) Protein sulfenic acids in redox signaling. Annu Rev Pharmacol Toxicol 44:325–347

    Article  PubMed  CAS  Google Scholar 

  220. Ostman A, Frijhoff J, Sandin A et al (2011) Regulation of protein tyrosine phosphatases by reversible oxidation. J Biochem 150:345–356

    Article  PubMed  CAS  Google Scholar 

  221. Salmeen A, Andersen JN, Myers MP et al (2003) Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423:769–773

    Article  PubMed  CAS  Google Scholar 

  222. van Montfort RL, Congreve M, Tisi D et al (2003) Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature 423:773–777

    Article  PubMed  CAS  Google Scholar 

  223. Yang J, Groen A, Lemeer S et al (2007) Reversible oxidation of the membrane distal domain of receptor PTPalpha is mediated by a cyclic sulfenamide. Biochemistry 46:709–719

    Article  PubMed  CAS  Google Scholar 

  224. Haque A, Andersen JN, Salmeen A et al (2011) Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit its phosphatase activity. Cell 147:185–198

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by NIH grants R03MH095532, R03MH084230, and R21CA132121 (to L.T.). We thank Robert Parker for his help in preparing Table 1.

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Authors and Affiliations

  1. Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

    Lutz Tautz

  2. Molecular Discovery Technologies, Bristol-Myers Squibb, Lawrenceville, NJ, USA

    David A. Critton

  3. Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

    Stefan Grotegut

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  1. Lutz Tautz
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  2. David A. Critton
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  3. Stefan Grotegut
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  1. Sanford Children's Health Research Ctr., Sanford-Burnham Medical Research Inst., North Torrey Pines Road 10901, La Jolla, 92037, California, USA

    José Luis Millán

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Tautz, L., Critton, D.A., Grotegut, S. (2013). Protein Tyrosine Phosphatases: Structure, Function, and Implication in Human Disease. In: Millán, J. (eds) Phosphatase Modulators. Methods in Molecular Biology, vol 1053. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-562-0_13

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