Challenges and opportunities in the development of protein phosphatase-directed therapeutics

ACS Chemical Biology

Volumn 8, Issue 1, 2013, Pages 36-45

  De Munter, Sofie ^a   Köhn, Maja ^b   Bollen, Mathieu ^a  

^a LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

^b EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHRAQUINONE; BISPEROXOVANADATE DERIVATIVE; BORTEZOMIB; CHAULMOOGRIC ACID; CP 320626; CYCLOSPORIN A; DIBENZO[B,D]FURAN MONOCARBOXYLIC ACID DERIVATIVE; FINGOLIMOD; FOSTRIECIN; GUANABENZ; L 158429; MENADIONE; MITOXANTRONE; NCGC 00241225; NCS 134149; NPLC 0393; PHOSPHONODIFLUOROMETHYL PHENYLALANINE DERIVATIVE; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE INHIBITOR; PURPURIN; QUINONE DERIVATIVE; R 164259; RABDOCOETSIN B; RABEPRAZOLE; S 349631; STIBOGLUCONATE SODIUM; TACROLIMUS; THIENOPYRIDONE; THIOETHER PEPTIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALLOSTERISM; CONFORMATIONAL TRANSITION; COVALENT BOND; DIMERIZATION; DRUG DESIGN; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEPHOSPHORYLATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; REVIEW;

DRUG DELIVERY SYSTEMS; HUMANS; PHOSPHOPROTEIN PHOSPHATASES; SMALL MOLECULE LIBRARIES;

EID: 84872502581     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb300597g     Document Type: Review

References (104)

1. Endicott, J. A., Noble, M. E., and Johnson, L. N. (2012) The structural basis for control of eukaryotic protein kinases Annu. Rev. Biochem. 81, 587-613
2. Zhang, J., Yang, P. L., and Gray, N. S. (2009) Targeting cancer with small molecule kinase inhibitors Nat. Rev. Cancer 9, 28-39
3. Knight, Z. A., Lin, H., and Shokat, K. M. (2010) Targeting the cancer kinome through polypharmacology Nat. Rev. Cancer 10, 130-137
4. Rabiller, M., Getlik, M., Kluter, S., Richters, A., Tuckmantel, S., Simard, J. R., and Rauh, D. (2010) Proteus in the world of proteins: conformational changes in protein kinases Arch. Pharm. (Weinheim) 343, 193-206
5. Poulikakos, P. I., Zhang, C., Bollag, G., Shokat, K. M., and Rosen, N. (2010) RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF Nature 464, 427-430
6. Zorn, J. A. and Wells, J. A. (2010) Turning enzymes ON with small molecules Nat. Chem. Biol. 6, 179-188
7. Moorhead, G. B., Trinkle-Mulcahy, L., and Ulke-Lemee, A. (2007) Emerging roles of nuclear protein phosphatases Nat. Rev. Mol. Cell Biol. 8, 234-244
8. Seifried, A., Schultz, J., and Gohla, A. (2012) Human HAD phosphatases: structure, mechanism, and roles in health and disease FEBS J. 10.1111/j.1742-4658.2012.08633.x
9. Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Osterman, A., Godzik, A., Hunter, T., Dixon, J., and Mustelin, T. (2004) Protein tyrosine phosphatases in the human genome Cell 117, 699-711 (Pubitemid 38748887)
10. Virshup, D. M. and Shenolikar, S. (2009) From promiscuity to precision: protein phosphatases get a makeover Mol. Cell 33, 537-545
11. Heroes, E., Lesage, B., Gornemann, J., Beullens, M., Van Meervelt, L., and Bollen, M. (2012) The PP1 binding code: a molecular-lego strategy that governs specificity FEBS J. 10.1111/j.1742-4658.2012.08547.x
12. Ostman, A., Hellberg, C., and Bohmer, F. D. (2006) Protein-tyrosine phosphatases and cancer Nat. Rev. Cancer 6, 307-320
13. Le Guezennec, X. and Bulavin, D. V. (2010) WIP1 phosphatase at the crossroads of cancer and aging Trends Biochem. Sci. 35, 109-114
14. Julien, S. G., Dube, N., Hardy, S., and Tremblay, M. L. (2011) Inside the human cancer tyrosine phosphatome Nat. Rev. Cancer 11, 35-49
15. Labbe, D. P., Hardy, S., and Tremblay, M. L. (2012) Protein tyrosine phosphatases in cancer: friends and foes! Prog. Mol. Biol. Transl. Sci. 106, 253-306
16. O'Neill, A. K., Niederst, M. J., and Newton, A. C. (2012) Suppression of survival signalling pathways by the phosphatase PHLPP FEBS J. 10.1111/j.1742-4658.2012.08537.x
17. Wang, Z., Shen, D., Parsons, D. W., Bardelli, A., Sager, J., Szabo, S., Ptak, J., Silliman, N., Peters, B. A., van der Heijden, M. S., Parmigiani, G., Yan, H., Wang, T. L., Riggins, G., Powell, S. M., Willson, J. K., Markowitz, S., Kinzler, K. W., Vogelstein, B., and Velculescu, V. E. (2004) Mutational analysis of the tyrosine phosphatome in colorectal cancers Science 304, 1164-1166 (Pubitemid 38661854)
18. Haesen, D., Sents, W., Ivanova, E., Lambrecht, C., and Janssens, V. (2012) Cellular inhibitors of Protein Phosphatase PP2A in cancer Biomed. Res. 23, 197-211
19. Hodis, E., Watson, I. R., Kryukov, G. V., Arold, S. T., Imielinski, M., Theurillat, J. P., Nickerson, E., Auclair, D., Li, L., Place, C., Dicara, D., Ramos, A. H., Lawrence, M. S., Cibulskis, K., Sivachenko, A., Voet, D., Saksena, G., Stransky, N., Onofrio, R. C., Winckler, W., Ardlie, K., Wagle, N., Wargo, J., Chong, K., Morton, D. L., Stemke-Hale, K., Chen, G., Noble, M., Meyerson, M., Ladbury, J. E., Davies, M. A., Gershenwald, J. E., Wagner, S. N., Hoon, D. S., Schadendorf, D., Lander, E. S., Gabriel, S. B., Getz, G., Garraway, L. A., and Chin, L. (2012) A landscape of driver mutations in melanoma Cell 150, 251-263
20. Ali, A. Y., Abedini, M. R., and Tsang, B. K. (2012) The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation Oncogene 31, 2175-2186
21. MacKeigan, J. P., Murphy, L. O., and Blenis, J. (2005) Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance Nat. Cell Biol. 7, 591-600 (Pubitemid 40796982)
22. Rato, S., Maia, S., Brito, P. M., Resende, L., Pereira, C. F., Moita, C., Freitas, R. P., Moniz-Pereira, J., Hacohen, N., Moita, L. F., and Goncalves, J. (2010) Novel HIV-1 knockdown targets identified by an enriched kinases/phosphatases shRNA library using a long-term iterative screen in Jurkat T-cells PLoS One 5, e9276
23. Zhang, J., Mendoza, M., Guiraldelli, M. F., Barbu, E. A., and Siraganian, R. P. (2010) Small interfering RNA screen for phosphatases involved in IgE-mediated mast cell degranulation J. Immunol. 184, 7178-7185
24. Yang, R., Lacson, R. G., Castriota, G., Zhang, X. D., Liu, Y., Zhao, W., Einstein, M., Camargo, L. M., Qureshi, S., Wong, K. K., Zhang, B. B., Ferrer, M., and Berger, J. P. (2012) A genome-wide siRNA screen to identify modulators of insulin sensitivity and gluconeogenesis PLoS One 7, e36384
25. Takemoto, A., Maeshima, K., Ikehara, T., Yamaguchi, K., Murayama, A., Imamura, S., Imamoto, N., Yokoyama, S., Hirano, T., Watanabe, Y., Hanaoka, F., Yanagisawa, J., and Kimura, K. (2009) The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A Nat. Struct. Mol. Biol. 16, 1302-1308
26. Yang, X., Dutta, U., and Shaw, L. M. (2010) SHP2 mediates the localized activation of Fyn downstream of the alpha6beta4 integrin to promote carcinoma invasion Mol. Cell. Biol. 30, 5306-5317
27. Song, M. S., Salmena, L., and Pandolfi, P. P. (2012) The functions and regulation of the PTEN tumour suppressor Nat. Rev. Mol. Cell Biol. 13, 283-296
28. Roy, J. and Cyert, M. S. (2009) Cracking the phosphatase code: docking interactions determine substrate specificity Sci. Signaling 2, re9
29. Tsaytler, P., Harding, H. P., Ron, D., and Bertolotti, A. (2011) Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis Science 332, 91-94
30. Boyce, M., Bryant, K. F., Jousse, C., Long, K., Harding, H. P., Scheuner, D., Kaufman, R. J., Ma, D., Coen, D. M., Ron, D., and Yuan, J. (2005) A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress Science 307, 935-939 (Pubitemid 40229232)
31. Krumbholz, M., Derfuss, T., Hohlfeld, R., and Meinl, E. (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy Nat. Rev. Neurol. 8, 613-623
32. Roberts, K. G., Smith, A. M., McDougall, F., Carpenter, H., Horan, M., Neviani, P., Powell, J. A., Thomas, D., Guthridge, M. A., Perrotti, D., Sim, A. T., Ashman, L. K., and Verrills, N. M. (2010) Essential requirement for PP2A inhibition by the oncogenic receptor c-KIT suggests PP2A reactivation as a strategy to treat c-KIT+ cancers Cancer Res. 70, 5438-5447
33. Wang, L., Wang, X., Chen, J., Yang, Z., Yu, L., Hu, L., and Shen, X. (2010) Activation of protein serine/threonine phosphatase PP2Calpha efficiently prevents liver fibrosis PLoS One 5, e14230
34. Aburai, N., Yoshida, M., Ohnishi, M., and Kimura, K. (2010) Sanguinarine as a potent and specific inhibitor of protein phosphatase 2C in vitro and induces apoptosis via phosphorylation of p38 in HL60 cells Biosci. Biotechnol. Biochem. 74, 548-552
35. Canals, D., Roddy, P., and Hannun, Y. A. (2012) Protein phosphatase 1alpha mediates ceramide-induced ERM protein dephosphorylation: a novel mechanism independent of phosphatidylinositol 4, 5-biphosphate (PIP2) and myosin/ERM phosphatase J. Biol. Chem. 287, 10145-10155
36. Perry, D. M., Kitatani, K., Roddy, P., El-Osta, M., and Hannun, Y. A. (2012) Identification and characterization of protein phosphatase 2C activation by ceramide J. Lipid Res. 53, 1513-1521
37. Tappan, E. and Chamberlin, A. R. (2008) Activation of protein phosphatase 1 by a small molecule designed to bind to the enzyme's regulatory site Chem. Biol. 15, 167-174 (Pubitemid 351253618)
38. Ammosova, T., Platonov, M., Yedavalli, V. R., Obukhov, Y., Gordeuk, V. R., Jeang, K. T., Kovalskyy, D., and Nekhai, S. (2012) Small molecules targeted to a non-catalytic ″RVxF″ binding site of protein phosphatase-1 inhibit HIV-1 PLoS One 7, e39481
39. Ramsey, A. J., Russell, L. C., and Chinkers, M. (2009) C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins Biochem. J. 423, 411-419
40. Cher, C., Tremblay, M. H., Barber, J. R., Chung Ng, S., and Zhang, B. (2010) Identification of chaulmoogric acid as a small molecule activator of protein phosphatase 5 Appl. Biochem. Biotechnol. 160, 1450-1459
41. Mattila, E., Marttila, H., Sahlberg, N., Kohonen, P., Tahtinen, S., Halonen, P., Perala, M., and Ivaska, J. (2010) Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase BMC Cancer 10, 7
42. Pautsch, A., Stadler, N., Wissdorf, O., Langkopf, E., Moreth, W., and Streicher, R. (2008) Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase J. Biol. Chem. 283, 8913-8918
43. Kelsall, I. R., Rosenzweig, D., and Cohen, P. T. (2009) Disruption of the allosteric phosphorylase a regulation of the hepatic glycogen-targeted protein phosphatase 1 improves glucose tolerance in vivo Cell. Signaling 21, 1123-1134
44. Zibrova, D., Grempler, R., Streicher, R., and Kauschke, S. G. (2008) Inhibition of the interaction between protein phosphatase 1 glycogen-targeting subunit and glycogen phosphorylase increases glycogen synthesis in primary rat hepatocytes Biochem. J. 412, 359-366 (Pubitemid 351758242)
45. Zhang, L. and Liu, H. (2010) Novel therapeutics based on inhibiting the interaction of glycogen phosphorylase and GL-subunit of glycogen-associated protein phosphatase 1: WO2009127723 Expert Opin. Ther. Pat. 20, 969-973
46. Ragusa, M. J., Dancheck, B., Critton, D. A., Nairn, A. C., Page, R., and Peti, W. (2010) Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites Nat. Struct. Mol. Biol. 17, 459-464
47. O'Connell, N., Nichols, S. R., Heroes, E., Beullens, M., Bollen, M., Peti, W., and Page, R. (2012) The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme Structure 20, 1746-1756
48. Bollen, M., Peti, W., Ragusa, M. J., and Beullens, M. (2010) The extended PP1 toolkit: designed to create specificity Trends Biochem. Sci. 35, 450-458
49. Brautigan, D. L. (2012) Protein Ser/Thr phosphatases-the ugly ducklings of cell signalling FEBS J. 10.1111/j.1742-4658.2012.08609.x
50. Niemela, M., Kauko, O., Sihto, H., Mpindi, J. P., Nicorici, D., Pernila, P., Kallioniemi, O. P., Joensuu, H., Hautaniemi, S., and Westermarck, J. (2012) CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes Oncogene 31, 4266-4278
51. Ma, L., Wen, Z. S., Liu, Z., Hu, Z., Ma, J., Chen, X. Q., Liu, Y. Q., Pu, J. X., Xiao, W. L., Sun, H. D., and Zhou, G. B. (2011) Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer PLoS One 6, e20159
52. Switzer, C. H., Cheng, R. Y., Vitek, T. M., Christensen, D. J., Wink, D. A., and Vitek, M. P. (2011) Targeting SET/I(2)PP2A oncoprotein functions as a multi-pathway strategy for cancer therapy Oncogene 30, 2504-2513
53. Christensen, D. J., Ohkubo, N., Oddo, J., Van Kanegan, M. J., Neil, J., Li, F., Colton, C. A., and Vitek, M. P. (2011) Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A J. Immunol. 186, 2535-2542
54. Mukhopadhyay, A., Saddoughi, S. A., Song, P., Sultan, I., Ponnusamy, S., Senkal, C. E., Snook, C. F., Arnold, H. K., Sears, R. C., Hannun, Y. A., and Ogretmen, B. (2009) Direct interaction between the inhibitor 2 and ceramide via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling FASEB J. 23, 751-763
55. Oaks, J. J., Mukhopadhyay, A., Santhanam, R., Saddoughi, S. A., Walker, C., Neviani, P., Harb, J. G., Ma, Y., Verstovsek, S., Marcucci, G., Briesewitz, R., Bittman, R., Chen, C. S., Quintas-Cardama, A., Ogretmen, B., and Perrotti, D. (2010) Pharmacologic restoration of PP2A activity and interference with the SET-PP2A interplay by FTY720 and its non-immunosuppressive derivative as a novel and efficient therapy for Ph-negative myeloproliferative disorders Blood 116, 340-340
56. Yang, Y., Huang, Q., Lu, Y. J., Li, X. Q., and Huang, S. A. (2012) Reactivating PP2A by FTY720 as a Novel therapy for AML with C-KIT tyrosine kinase domain mutation J. Cell. Biochem. 113, 1314-1322
57. Chen, K. F., Liu, C. Y., Lin, Y. C., Yu, H. C., Liu, T. H., Hou, D. R., Chen, P. J., and Cheng, A. L. (2010) CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells Oncogene 29, 6257-6266
58. Chen, K. F., Yu, H. C., Liu, C. Y., Chen, H. J., Chen, Y. C., Hou, D. R., Chen, P. J., and Cheng, A. L. (2011) Bortezomib sensitizes HCC cells to CS-1008, an antihuman death receptor 5 antibody, through the inhibition of CIP2A Mol. Cancer Ther. 10, 892-901
59. Tseng, L. M., Liu, C. Y., Chang, K. C., Chu, P. Y., Shiau, C. W., and Chen, K. F. (2012) CIP2A is a target of bortezomib in human triple negative breast cancer cells Breast Cancer Res. 14, R68
60. Chen, K. F., Yu, H. C., Liu, T. H., Lee, S. S., Chen, P. J., and Cheng, A. L. (2010) Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation J. Hepatol. 52, 88-95
61. Chatterjee, J., Beullens, M., Sukackaite, R., Qian, J., Lesage, B., Hart, D. J., Bollen, M., and Köhn, M. (2012) Development of a Peptide that Selectively Activates Protein Phosphatase-1 in Living Cells Angew. Chem., Int. Ed. 51, 10054-10059
62. Paduano, F., Ortuso, F., Campiglia, P., Raso, C., Iaccino, E., Gaspari, M., Gaudio, E., Mangone, G., Carotenuto, A., Bilotta, A., Narciso, D., Palmieri, C., Agosti, V., Artese, A., Gomez-Monterrey, I., Sala, M., Cuda, G., Iuliano, R., Perrotti, N., Scala, G., Viglietto, G., Alcaro, S., Croce, C. M., Novellino, E., Fusco, A., and Trapasso, F. (2012) Isolation and functional characterization of peptide agonists of PTPRJ, a tyrosine phosphatase receptor endowed with tumor suppressor Activity ACS Chem. Biol. 7, 1666-1676
63. Zhang, S. and Zhang, Z. Y. (2007) PTP1B as a drug target: recent developments in PTP1B inhibitor discovery Drug Discovery Today 12, 373-381 (Pubitemid 46636379)
64. Erbe, D. V., Klaman, L. D., Wilson, D. P., Wan, Z. K., Kirincich, S. J., Will, S., Xu, X., Kung, L., Wang, S., Tam, S., Lee, J., and Tobin, J. F. (2009) Prodrug delivery of novel PTP1B inhibitors to enhance insulin signalling Diabetes, Obes. Metab. 11, 579-588
65. Vintonyak, V. V., Antonchick, A. P., Rauh, D., and Waldmann, H. (2009) The therapeutic potential of phosphatase inhibitors Curr. Opin. Chem. Biol. 13, 272-283
66. He, R., Zeng, L. F., He, Y., Zhang, S., and Zhang, Z. Y. (2012) Small molecule tools for functional interrogation of protein tyrosine phosphatases FEBS J. 10.1111/j.1742-4658.2012.08718.x
67. Sobhia, M. E., Paul, S., Shinde, R., Potluri, M., Gundam, V., Kaur, A., and Haokip, T. (2012) Protein tyrosine phosphatase inhibitors: a patent review (2002-2011) Expert Opin. Ther. Pat. 22, 125-153
68. Haque, A., Andersen, J. N., Salmeen, A., Barford, D., and Tonks, N. K. (2011) Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit its phosphatase activity Cell 147, 185-198
69. Boutselis, I. G., Yu, X., Zhang, Z. Y., and Borch, R. F. (2007) Synthesis and cell-based activity of a potent and selective protein tyrosine phosphatase 1B inhibitor prodrug J. Med. Chem. 50, 856-864 (Pubitemid 46332997)
70. Zhang, S., Liu, S., Tao, R., Wei, D., Chen, L., Shen, W., Yu, Z. H., Wang, L., Jones, D. R., Dong, X. C., and Zhang, Z. Y. (2012) A Highly Selective and Potent PTP-MEG2 Inhibitor with Therapeutic Potential for Type 2 Diabetes J. Am. Chem. Soc. 134, 18116-18124
71. Zhang, S., Chen, L., Luo, Y., Gunawan, A., Lawrence, D. S., and Zhang, Z. Y. (2009) Acquisition of a potent and selective TC-PTP inhibitor via a stepwise fluorophore-tagged combinatorial synthesis and screening strategy J. Am. Chem. Soc. 131, 13072-13079
72. Aceto, N., Sausgruber, N., Brinkhaus, H., Gaidatzis, D., Martiny-Baron, G., Mazzarol, G., Confalonieri, S., Quarto, M., Hu, G., Balwierz, P. J., Pachkov, M., Elledge, S. J., van Nimwegen, E., Stadler, M. B., and Bentires-Alj, M. (2012) Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop Nat. Med. 18, 529-537
73. Lavecchia, A., Giovanni, C. D., and Novellino, E. (2012) CDC25 phosphatase inhibitors: an update Mini Rev. Med. Chem. 12, 62-73
74. Al-Aidaroos, A. Q. and Zeng, Q. (2010) PRL-3 phosphatase and cancer metastasis J. Cell. Biochem. 111, 1087-1098
75. Rios, P., Li, X., and Köhn, M. (2012) Molecular mechanisms of the PRL phosphatases FEBS J. 10.1111/j.1742-4658.2012.08565.x
76. Naing, A., Reuben, J. M., Camacho, L. H., Gao, H., Lee, B. N., Cohen, E. N., Verschraegen, C., Stephen, S., Aaron, J., Hong, D., Wheler, J., and Kurzrock, R. (2011) Phase I dose escalation study of sodium stibogluconate (SSG), a protein tyrosine phosphatase inhibitor, combined with interferon alpha for patients with solid tumors J. Cancer 2, 81-89
77. Mali, R. S., Ma, P., Zeng, L. F., Martin, H., Ramdas, B., He, Y., Sims, E., Nabinger, S., Ghosh, J., Sharma, N., Munugalavadla, V., Chatterjee, A., Li, S., Sandusky, G., Craig, A. W., Bunting, K. D., Feng, G. S., Chan, R. J., Zhang, Z. Y., and Kapur, R. (2012) Role of SHP2 phosphatase in KIT-induced transformation: identification of SHP2 as a druggable target in diseases involving oncogenic KIT Blood 120, 2669-2678
78. Daouti, S., Li, W. H., Qian, H., Huang, K. S., Holmgren, J., Levin, W., Reik, L., McGady, D. L., Gillespie, P., Perrotta, A., Bian, H., Reidhaar-Olson, J. F., Bliss, S. A., Olivier, A. R., Sergi, J. A., Fry, D., Danho, W., Ritland, S., Fotouhi, N., Heimbrook, D., and Niu, H. (2008) A selective phosphatase of regenerating liver phosphatase inhibitor suppresses tumor cell anchorage-independent growth by a novel mechanism involving p130Cas cleavage Cancer Res. 68, 1162-1169 (Pubitemid 351272235)
79. Han, Y. M., Lee, S. K., Jeong, D. G., Ryu, S. E., Han, D. C., Kim, D. K., and Kwon, B. M. (2012) Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of PRL-3 phosphatase activity Bioorg. Med. Chem. Lett. 22, 323-326
80. Guo, K., Tang, J. P., Jie, L., Al-Aidaroos, A. Q., Hong, C. W., Tan, C. P., Park, J. E., Varghese, L., Feng, Z., Zhou, J., Chng, W. J., and Zeng, Q. (2012) Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice Oncotarget 3, 158-171
81. Lee, K. and Burke, T. R., Jr. (2003) CD45 protein-tyrosine phosphatase inhibitor development Curr. Top. Med. Chem. 3, 797-807
82. Stanford, S. M., Panchal, R. G., Walker, L. M., Wu, D. J., Falk, M. D., Mitra, S., Damle, S. S., Ruble, D., Kaltcheva, T., Zhang, S., Zhang, Z. Y., Bavari, S., Barrios, A. M., and Bottini, N. (2012) High-throughput screen using a single-cell tyrosine phosphatase assay reveals biologically active inhibitors of tyrosine phosphatase CD45 Proc. Natl. Acad. Sci. U.S.A. 109, 13972-13977
83. Vang, T., Liu, W. H., Delacroix, L., Wu, S., Vasile, S., Dahl, R., Yang, L., Musumeci, L., Francis, D., Landskron, J., Tasken, K., Tremblay, M. L., Lie, B. A., Page, R., Mustelin, T., Rahmouni, S., Rickert, R. C., and Tautz, L. (2012) LYP inhibits T-cell activation when dissociated from CSK Nat. Chem. Biol. 8, 437-446
84. Keyes, K. T., Xu, J., Long, B., Zhang, C., Hu, Z., and Ye, Y. (2010) Pharmacological inhibition of PTEN limits myocardial infarct size and improves left ventricular function postinfarction Am. J. Physiol. Heart Circ. Physiol. 298, H1198-1208
85. Dal Ponte, C., Alchera, E., Follenzi, A., Imarisio, C., Prat, M., Albano, E., and Carini, R. (2011) Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury Liver Transpl. 17, 474-482
86. McConnell, J. L. and Wadzinski, B. E. (2009) Targeting protein serine/threonine phosphatases for drug development Mol. Pharmacol. 75, 1249-1261
87. Swingle, M. R., Amable, L., Lawhorn, B. G., Buck, S. B., Burke, C. P., Ratti, P., Fischer, K. L., Boger, D. L., and Honkanen, R. E. (2009) Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and(beta12-beta13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors J. Pharmacol. Exp. Ther. 331, 45-53
88. Guan, M., Zhou, Y., Zhu, Q. L., Liu, Y., Bei, Y. Y., Zhang, X. N., and Zhang, Q. (2012) N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy Nanomedicine 8, 1172-1181
89. Kranias, E. G. and Hajjar, R. J. (2012) Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome Circ. Res. 110, 1646-1660
90. Zhang, M., Cho, E. J., Burstein, G., Siegel, D., and Zhang, Y. (2011) Selective inactivation of a human neuronal silencing phosphatase by a small molecule inhibitor ACS Chem. Biol. 6, 511-519
91. Krueger, A. B., Dehdashti, S. J., Southall, N., Marugan, J. J., Ferrer, M., Li, X., Ford, H. L., Zheng, W., and Zhao, R. (2012) Identification of a Selective Small-Molecule Inhibitor Series Targeting the Eyes Absent 2 (Eya2) Phosphatase Activity J. Biomol. Screen. 10.1177/1087057112453936
92. Sierecki, E., Sinko, W., McCammon, J. A., and Newton, A. C. (2010) Discovery of small molecule inhibitors of the PH domain leucine-rich repeat protein phosphatase (PHLPP) by chemical and virtual screening J. Med. Chem. 53, 6899-6911
93. Hayashi, R., Tanoue, K., Durell, S. R., Chatterjee, D. K., Jenkins, L. M., Appella, D. H., and Appella, E. (2011) Optimization of a cyclic peptide inhibitor of Ser/Thr phosphatase PPM1D (Wip1) Biochemistry (Mosc.) 50, 4537-4549
94. Barr, A. J., Ugochukwu, E., Lee, W. H., King, O. N., Filippakopoulos, P., Alfano, I., Savitsky, P., Burgess-Brown, N. A., Muller, S., and Knapp, S. (2009) Large-scale structural analysis of the classical human protein tyrosine phosphatome Cell 136, 352-363
95. Dunker, A. K. and Uversky, V. N. (2010) Drugs for 'protein clouds': targeting intrinsically disordered transcription factors Curr. Opin. Pharmacol. 10, 782-788
96. Grassie, M. E., Moffat, L. D., Walsh, M. P., and MacDonald, J. A. (2011) The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1delta Arch. Biochem. Biophys. 510, 147-159
97. Hinke, S. A., Navedo, M. F., Ulman, A., Whiting, J. L., Nygren, P. J., Tian, G., Jimenez-Caliani, A. J., Langeberg, L. K., Cirulli, V., Tengholm, A., Dell'acqua, M. L., Santana, L. F., and Scott, J. D. (2012) Anchored phosphatases modulate glucose homeostasis EMBO J. 31, 3991-4004
98. Suijkerbuijk, S. J., Vleugel, M., Teixeira, A., and Kops, G. J. (2012) Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments Dev. Cell 23, 745-755
99. Fuller, J. C., Burgoyne, N. J., and Jackson, R. M. (2009) Predicting druggable binding sites at the protein-protein interface Drug Discovery Today 14, 155-161
100. Tonks, N. K. (2006) Protein tyrosine phosphatases: from genes, to function, to disease Nat. Rev. Mol. Cell Biol. 7, 833-846 (Pubitemid 44627477)
101. Shi, Y. (2009) Assembly and structure of protein phosphatase 2A Sci. China C Life Sci. 52, 135-146
102. Bollen, M., Gerlich, D. W., and Lesage, B. (2009) Mitotic phosphatases: from entry guards to exit guides Trends Cell Biol. 19, 531-541
103. Lu, X., Nguyen, T. A., Moon, S. H., Darlington, Y., Sommer, M., and Donehower, L. A. (2008) The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways Cancer Metastasis Rev. 27, 123-135
104. Das, A. K., Helps, N. R., Cohen, P. T., and Barford, D. (1996) Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution EMBO J. 15, 6798-6809