Protein tyrosine phosphatases: Structure, function, and implication in human disease

Methods in Molecular Biology

Volumn 1053, Issue , 2013, Pages 179-221

  Tautz, Lutz ^a   Critton, David A ^b   Grotegut, Stefan ^a  

^a BURNHAM INSTITUTE   (United States)

^b BRISTOL MYERS SQUIBB   (United States)

Author keywords

Function; Human disease; Inhibitors; Phosphatases; PTP; PTP1B; SHP2; Specificity; Structure; Substrate recognition; Tyrosine phosphorylation

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE 1B; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PROTEIN TYROSINE PHOSPHATASE SHP 2; STRIATAL ENRICHED PROTEIN TYROSINE PHOSPHATASE; THREONINE; UNCLASSIFIED DRUG;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; BREAST CANCER; CARCINOGENESIS; CATALYSIS; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE; GENE; HEMATOPOIETIC CELL; HUMAN; JUVENILE MYELOMONOCYTIC LEUKEMIA; METABOLIC DISORDER; MOLECULAR RECOGNITION; NONHUMAN; NUCLEOPHILICITY; NUCLEOTIDE SEQUENCE; OBESITY; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN DOMAIN; PROTEIN FUNCTION; SITE DIRECTED MUTAGENESIS; UNINDEXED SEQUENCE; X RAY CRYSTALLOGRAPHY;

CATALYSIS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; NEOPLASMS; PHOSPHORYLATION; PROTEIN TYROSINE PHOSPHATASES; SUBSTRATE SPECIFICITY; TYROSINE;

EID: 84881087345     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-62703-562-0_13     Document Type: Article

References (224)

1. Hunter T (2000) Signaling-2000 and beyond. Cell 100:113-127
2. Pawson T, Scott JD (2005) Protein phosphorylation in signaling-50 years and counting. Trends Biochem Sci 30:286-290
3. Luan S (2003) Protein phosphatases in plants. Annu Rev Plant Biol 54:63-92
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
5. Feher Z, Szirak K (1999) Signal transduction in fungi-The role of protein phosphorylation. Acta Microbiol Immunol Hung 46:269-271
6. Moorhead GB, De Wever V, Templeton G et al (2009) Evolution of protein phosphatases in plants and animals. Biochem J 417:401-409
7. Olsen JV, Blagoev B, Gnad F et al (2006) Global, in vivo, and site-specifi c phosphorylation dynamics in signaling networks. Cell 127:635-648
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
9. Hunter T (1998) The role of tyrosine phosphorylation in cell growth and disease. Harvey Lect 94:81-119
10. Larsen M, Tremblay ML, Yamada KM (2003) Phosphatases in cell-matrix adhesion and migration. Nat Rev Mol Cell Biol 4:700-711
11. Alonso A, Sasin J, Bottini N et al (2004) Protein tyrosine phosphatases in the human genome. Cell 117:699-711
12. Mustelin T, Vang T, Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5:43-57
13. Tonks NK (2006) Protein tyrosine phosphatases: From genes, to function, to disease. Nat Rev Mol Cell Biol 7:833-846
14. Halle M, Tremblay ML, Meng TC (2007) Protein tyrosine phosphatases: Emerging regulators of apoptosis. Cell Cycle 6:2773-2781
15. Pao LI, Badour K, Siminovitch KA et al (2007) Nonreceptor protein-Tyrosine phosphatases in immune cell signaling. Annu Rev Immunol 25:473-523
16. Hunter T (2009) Tyrosine phosphorylation: Thirty years and counting. Curr Opin Cell Biol 21:140-146
17. Rhee I, Veillette A (2012) Protein tyrosine phosphatases in lymphocyte activation and autoimmunity. Nat Immunol 13:439-447
18. Cohen P (2002) Protein kinases-The major drug targets of the twenty-fi rst century? Nat Rev Drug Discov 1:309-315
19. Tautz L, Pellecchia M, Mustelin T (2006) Targeting the PTPome in human disease. Expert Opin Ther Targets 10:157-177
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
21. Pulido R, Hooft van Huijsduijnen R (2008) Protein tyrosine phosphatases: Dual-specifi city phosphatases in health and disease. FEBS J 275:848-866
22. Patterson KI, Brummer T, O'Brien PM et al (2009) Dual-specifi city phosphatases: Critical regulators with diverse cellular targets. Biochem J 418:475-489
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
24. Zhang ZY, Wang Y, Dixon JE (1994) Dissecting the catalytic mechanism of proteintyrosine phosphatases. Proc Natl Acad Sci U S A 91:1624-1627
25. Zhang ZY (1995) Kinetic and mechanistic characterization of a mammalian proteintyrosine phosphatase, PTP1. J Biol Chem 270:11199-11204
26. Denu JM, Stuckey JA, Saper MA et al (1996) Form and function in protein dephosphorylation. Cell 87:361-364
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
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
29. Hengge AC, Denu JM, Dixon JE (1996) Transition-state structures for the native dualspecifi c phosphatase VHR and D92N and S131A mutants. Contributions to the driving force for catalysis. Biochemistry 35: 7084-7092
30. Zhang ZY (2002) Protein tyrosine phosphatases, structure and function, substrate specifi city, and inhibitor development. Annu Rev Pharmacol Toxicol 42:209-234
31. Zhang ZY, Maclean D, McNamara DJ et al (1994) Protein tyrosine phosphatase substrate specifi city: Size and phosphotyrosine positioning requirements in peptide substrates. Biochemistry 33:2285-2290
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
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
34. Wiesmann C, Barr KJ, Kung J et al (2004) Allosteric inhibition of protein tyrosine phosphatase 1B. Nat Struct Mol Biol 11:730-737
35. Kamerlin SC, Rucker R, Boresch S (2007) A molecular dynamics study of WPD-loop fl exibility in PTP1B. Biochem Biophys Res Commun 356:1011-1016
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
37. Lorenz U (2009) SHP-1 and SHP-2 in T cells: Two phosphatases functioning at many levels. Immunol Rev 228:342-359
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
39. Hof P, Pluskey S, Dhe-Paganon S et al (1998) Crystal structure of the tyrosine phosphatase SHP-2. Cell 92:441-450
40. Johnson P, Ostergaard HL, Wasden C et al (1992) Mutational analysis of CD45. A leukocyte-specifi c protein tyrosine phosphatase. J Biol Chem 267:8035-8041
41. Streuli M, Krueger NX, Thai T et al (1990) Distinct functional roles of the two intracellular phosphatase like domains of the receptorlinked protein tyrosine phosphatases LCA and LAR. EMBO J 9:2399-2407
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
43. Shi Y (2009) Serine/threonine phosphatases: Mechanism through structure. Cell 139: 468-484
44. Barford D, Flint AJ, Tonks NK (1994) Crystal structure of human protein tyrosine phosphatase 1B. Science 263:1397-1404
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
46. Tonks NK (2005) Redox redux: Revisiting PTPs and the control of cell signaling. Cell 121:667-670
47. Chen YY, Chu HM, Pan KT et al (2008) Cysteine S-nitrosylation protects proteintyrosine phosphatase 1B against oxidationinduced permanent inactivation. J Biol Chem 283:35265-35272
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
49. Keng YF, Wu L, Zhang ZY (1999) Probing the function of the conserved tryptophan in the fl exible loop of the Yersinia protein-Tyrosine phosphatase. Eur J Biochem 259:809-814
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
51. Kurkcuoglu Z, Bakan A, Kocaman D et al (2012) Coupling between catalytic loop motions and enzyme global dynamics. PLoS Comput Biol 8:e1002705
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
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
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
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
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
57. Rabin DU, Pleasic SM, Shapiro JA et al (1994) Islet cell antigen 512 is a diabetesspecifi c islet autoantigen related to protein tyrosine phosphatases. J Immunol 152: 3183-3188
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
59. Eswaran J, von Kries JP, Marsden B et al (2006) Crystal structures and inhibitor identifi cation for PTPN5, PTPRR and PTPN7: A family of human MAPK-specifi c protein tyrosine phosphatases. Biochem J 395:483-491
60. Iversen LF, Moller KB, Pedersen AK et al (2002) Structure determination of T cell protein-Tyrosine phosphatase. J Biol Chem 277:19982-19990
61. Yang J, Cheng Z, Niu T et al (2000) Structural basis for substrate specifi city of proteintyrosine phosphatase SHP-1. J Biol Chem 275:4066-4071
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
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
64. Xie L, Zhang YL, Zhang ZY (2002) Design and characterization of an improved protein tyrosine phosphatase substrate-Trapping mutant. Biochemistry 41:4032-4039
65. Zhao Y, Wu L, Noh SJ et al (1998) Altering the nucleophile specifi city of a proteintyrosine phosphatase-catalyzed reaction. Probing the function of the invariant glutamine residues. J Biol Chem 273:5484-5492
66. Pedersen AK, Guo XL, Moller KB et al (2004) Residue 182 infl uences the second step of protein-Tyrosine phosphatase-mediated catalysis. Biochem J 378:421-433
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
68. Bryson GL, Massa H, Trask BJ et al (1995) Gene structure, sequence, and chromosomal localization of the human red cell-Type lowmolecular-weight acid phosphotyrosyl phosphatase gene, ACP1. Genomics 30:133-140
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
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
71. Rudolph J (2007) Cdc25 phosphatases: Structure, specifi city, and mechanism. Biochemistry 46:3595-3604
72. Mailand N, Falck J, Lukas C et al (2000) Rapid destruction of human Cdc25A in response to DNA damage. Science 288: 1425-1429
73. Donzelli M, Squatrito M, Ganoth D et al (2002) Dual mode of degradation of Cdc25 A phosphatase. EMBO J 21:4875-4884
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
75. Forrest A, Gabrielli B (2001) Cdc25B activity is regulated by 14-3-3. Oncogene 20: 4393-4401
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
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-Amplifi cation of MPF at mitosis. EMBO J 12:53-63
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
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
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
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
82. Sarmiento M, Zhao Y, Gordon SJ et al (1998) Molecular basis for substrate specifi city of protein-Tyrosine phosphatase 1B. J Biol Chem 273:26368-26374
83. Huang Z, Zhou B, Zhang ZY (2004) Molecular determinants of substrate recognition in hematopoietic protein-Tyrosine phosphatase. J Biol Chem 279:52150-52159
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
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
86. Wiland AM, Denu JM, Mourey RJ et al (1996) Purifi cation and kinetic characterization of the mitogen-Activated protein kinase phosphatase rVH6. J Biol Chem 271: 33486-33492
87. Zhao Y, Zhang ZY (2001) The mechanism of dephosphorylation of extracellular signalregulated kinase 2 by mitogen-Activated protein kinase phosphatase 3. J Biol Chem 276:32382-32391
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
89. Puius YA, Zhao Y, Sullivan M et al (1997) Identifi cation of a second aryl phosphatebinding site in protein-Tyrosine phosphatase 1B: A paradigm for inhibitor design. Proc Natl Acad Sci U S A 94:13420-13425
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
91. Peters GH, Iversen LF, Branner S et al (2000) Residue 259 is a key determinant of substrate specifi city of protein-Tyrosine phosphatases 1B and alpha. J Biol Chem 275: 18201-18209
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
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
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
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
96. Garton AJ, Flint AJ, Tonks NK (1996) Identifi cation of p130(cas) as a substrate for the cytosolic protein tyrosine phosphatase PTP-PEST. Mol Cell Biol 16:6408-6418
97. Blanchetot C, Chagnon M, Dube N et al (2005) Substrate-Trapping techniques in the identifi cation of cellular PTP targets. Methods 35:44-53
98. Agazie YM, Hayman MJ (2003) Development of an effi cient "substrate-Trapping" mutant of Src homology phosphotyrosine phosphatase 2 and identifi cation of the epidermal growth factor receptor, Gab1, and three other proteins as target substrates. J Biol Chem 278:13952-13958
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
100. Buhrman G, Parker B, Sohn J et al (2005) Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfi de bond. Biochemistry 44:5307-5316
101. Ostman A, Hellberg C, Bohmer FD (2006) Protein-Tyrosine phosphatases and cancer. Nat Rev Cancer 6:307-320
102. Vang T, Miletic AV, Arimura Y et al (2008) Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol 26:29-55
103. Julien SG, Dube N, Hardy S et al (2011) Inside the human cancer tyrosine phosphatome. Nat Rev Cancer 11:35-49
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
105. Keniry M, Parsons R (2008) The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 27: 5477-5485
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
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
108. Mohi MG, Neel BG (2007) The role of Shp2 (PTPN11) in cancer. Curr Opin Genet Dev 17:23-30
109. Xu R (2007) Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia. Cell Res 17:295-297
110. Saha S, Bardelli A, Buckhaults P et al (2001) A phosphatase associated with metastasis of colorectal cancer. Science 294:1343-1346
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
112. Jiang ZX, Zhang ZY (2008) Targeting PTPs with small molecule inhibitors in cancer treatment. Cancer Metastasis Rev 27:263-272
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
114. Julien SG, Dube N, Read M et al (2007) Protein tyrosine phosphatase 1B defi ciency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat Genet 39:338-346
115. Bentires-Alj M, Neel BG (2007) Proteintyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res 67:2420-2424
116. Tonks NK, Muthuswamy SK (2007) A brake becomes an accelerator: PTP1B-A new therapeutic target for breast cancer. Cancer Cell 11:214-216
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
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
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
120. Stanford SM, Mustelin TM, Bottini N (2010) Lymphoid tyrosine phosphatase and autoimmunity: Human genetics rediscovers tyrosine phosphatases. Semin Immunopathol 32: 127-136
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
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
123. Zanke B, Squire J, Griesser H et al (1994) A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplifi ed and overexpressed in myeloid malignancies maps to chromosome 1q32.1. Leukemia 8:236-244
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
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
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
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
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
129. Laporte J, Hu LJ, Kretz C et al (1996) A gene mutated in X-linked myotubular myopathy defi nes a new putative tyrosine phosphatase family conserved in yeast. Nat Genet 13: 175-182
130. Bolino A, Muglia M, Conforti FL et al (2000) Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularinrelated protein-2. Nat Genet 25:17-19
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
132. Kung C, Pingel JT, Heikinheimo M et al (2000) Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodefi ciency disease. Nat Med 6: 343-345
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
134. Zhang S, Zhang ZY (2007) PTP1B as a drug target: Recent developments in PTP1B inhibitor discovery. Drug Discov Today 12: 373-381
135. Lee S, Wang Q (2007) Recent development of small molecular specifi c inhibitor of protein tyrosine phosphatase 1B. Med Res Rev 27:553-573
136. Barr AJ (2010) Protein tyrosine phosphatases as drug targets: Strategies and challenges of inhibitor development. Future Med Chem 2:1563-1576
137. Popov D (2011) Novel protein tyrosine phosphatase 1B inhibitors: Interaction requirements for improved intracellular effi cacy in type 2 diabetes mellitus and obesity control. Biochem Biophys Res Commun 410: 377-381
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
139. Tanner MM, Grenman S, Koul A et al (2000) Frequent amplifi cation of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res 6:1833-1839
140. Ginestier C, Cervera N, Finetti P et al (2006) Prognosis and gene expression profi ling of 20q13-Amplifi ed breast cancers. Clin Cancer Res 12:4533-4544
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
142. Zhai YF, Beittenmiller H, Wang B et al (1993) Increased expression of specifi c protein tyrosine phosphatases in human breast epithelial cells neoplastically transformed by the neu oncogene. Cancer Res 53:2272-2278
143. Bjorge JD, Pang A, Fujita DJ (2000) Identifi cation 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
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
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
146. Dadke S, Chernoff J (2003) Protein-Tyrosine phosphatase 1B mediates the effects of insulin on the actin cytoskeleton in immortalized fi broblasts. J Biol Chem 278:40607-40611
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
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
149. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: Correlation of relapse and survival with amplifi cation of the HER-2/ neu oncogene. Science 235:177-182
150. Bange J, Zwick E, Ullrich A (2001) Molecular targets for breast cancer therapy and prevention. Nat Med 7:548-552
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
152. Nahta R, Esteva FJ (2007) Trastuzumab: Triumphs and tribulations. Oncogene 26: 3637-3643
153. Grossmann KS, Rosario M, Birchmeier C et al (2010) The tyrosine phosphatase Shp2 in development and cancer. Adv Cancer Res 106:53-89
154. Liu X, Qu CK (2011) Protein tyrosine phosphatase SHP-2 (PTPN11) in hematopoiesis and leukemogenesis. J Signal Transduct 2011:195-239
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
156. Noonan JA (1968) Hypertelorism with turner phenotype. a new syndrome with associated congenital heart disease. Am J Dis Child 116: 373-380
157. Allanson JE (1987) Noonan syndrome. J Med Genet 24:9-13
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
159. Opitz JM (1985) The Noonan syndrome. Am J Med Genet 21:515-518
160. Tartaglia M, Gelb BD (2005) Noonan syndrome and related disorders: Genetics and pathogenesis. Annu Rev Genomics Hum Genet 6:45-68
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
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
163. Chan RJ, Feng GS (2007) PTPN11 is the fi rst identifi ed proto-oncogene that encodes a tyrosine phosphatase. Blood 109:862-867
164. Chan G, Kalaitzidis D, Neel BG (2008) The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev 27:179-192
165. Barford D, Neel BG (1998) Revealing mechanisms for SH2 domain mediated regulation of the protein tyrosine phosphatase SHP-2. Structure 6:249-254
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
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
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
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
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
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
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
173. Schubbert S, Zenker M, Rowe SL et al (2006) Germline KRAS mutations cause Noonan syndrome. Nat Genet 38:331-336
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
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
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
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
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
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
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
181. Loh ML (2011) Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol 152:677-687
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
183. Chen L, Sung SS, Yip ML et al (2006) Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol 70:562-570
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
185. Hellmuth K, Grosskopf S, Lum CT et al (2008) Specifi c inhibitors of the protein tyrosine phosphatase Shp2 identifi ed by highthroughput docking. Proc Natl Acad Sci U S A 105:7275-7280
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
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
188. Liu S, Yu Z, Yu X et al (2011) SHP2 is a target of the immunosuppressant tautomycetin. Chem Biol 18:101-110
189. Baum ML, Kurup P, Xu J et al (2010) A STEP forward in neural function and degeneration. Commun Integr Biol 3:419-422
190. Zhang Y, Kurup P, Xu J et al (2010) Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular defi cits in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 107: 19014-19019
191. Snyder EM, Nong Y, Almeida CG et al (2005) Regulation of NMDA receptor traffi cking by amyloid-beta. Nat Neurosci 8:1051-1058
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
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
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
195. Hardy JA, Higgins GA (1992) Alzheimer's disease: The amyloid cascade hypothesis. Science 256:184-185
196. Selkoe DJ (1991) The molecular pathology of Alzheimer's disease. Neuron 6:487-498
197. Kurup P, Zhang Y, Xu J et al (2010) Abetamediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61. J Neurosci 30:5948-5957
198. Bialy L, Waldmann H (2005) Inhibitors of protein tyrosine phosphatases: Nextgeneration drugs? Angew Chem Int Ed Engl 44:3814-3839
199. Vintonyak VV, Antonchick AP, Rauh D et al (2009) The therapeutic potential of phosphatase inhibitors. Curr Opin Chem Biol 13: 272-283
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
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
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
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
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
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
206. Yu X, Sun JP, He Y et al (2007) Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specifi c tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A 104:19767-19772
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
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
209. Zhang XY, Bishop AC (2007) Site-specifi c incorporation of allosteric-inhibition sites in a protein tyrosine phosphatase. J Am Chem Soc 129:3812-3813
210. Tautz L, Mustelin T (2007) Strategies for developing protein tyrosine phosphatase inhibitors. Methods 42:250-260
211. Pot DA, Dixon JE (1992) Active site labeling of a receptor-like protein tyrosine phosphatase. J Biol Chem 267:140-143
212. Zhang ZY, Davis JP, Van Etten RL (1992) Covalent modifi cation and active site-directed inactivation of a low molecular weight phosphotyrosyl protein phosphatase. Biochemistry 31:1701-1711
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
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 Cu 2+ ion. Arch Biochem Biophys 382:72-80
215. Niesen FH, Berglund H, Vedadi M (2007) The use of differential scanning fl uorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2:2212-2221
216. Rhee SG, Chang TS, Bae YS et al (2003) Cellular regulation by hydrogen peroxide. J Am Soc Nephrol 14:S211-S215
217. Miki H, Funato Y (2012) Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species. J Biochem 151:255-261
218. Roos G, Messens J (2011) Protein sulfenic acid formation: From cellular damage to redox regulation. Free Radic Biol Med 51: 314-326
219. Poole LB, Karplus PA, Claiborne A (2004) Protein sulfenic acids in redox signaling. Annu Rev Pharmacol Toxicol 44:325-347
220. Ostman A, Frijhoff J, Sandin A et al (2011) Regulation of protein tyrosine phosphatases by reversible oxidation. J Biochem 150: 345-356
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
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
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
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