Small molecule tools for functional interrogation of protein tyrosine phosphatases

The importance of protein tyrosine phosphatases (PTPs) in the regulation of cellular signalling is well established. Malfunction of PTP activity is also known to be associated with cancer, metabolic syndromes and autoimmune disorders, as well as neurodegenerative and infectious diseases. However, a detailed understanding of the roles played by the PTPs in normal physiology and in pathogenic conditions has been hampered by the absence of PTP‐specific small molecule agents. In addition, the therapeutic benefits of modulating this target class are underexplored as a result of a lack of suitable chemical probes. Potent and specific PTP inhibitors could significantly facilitate functional analysis of the PTPs in complex cellular signal transduction pathways and may constitute valuable therapeutics in the treatment of several human diseases. We highlight the current challenges to and opportunities for developing PTP‐specific small molecule agents. We also review available selective small molecule inhibitors developed for a number of PTPs, including PTP1B, TC‐PTP, SHP2, lymphoid‐specific tyrosine phosphatase, haematopoietic protein tyrosine phosphatase, CD45, PTPβ, PTPγ, PTPRO, Vaccinia H1‐related phosphatase, mitogen‐activated protein kinase phosphatase‐1, mitogen‐activated protein kinase phosphatase‐3, Cdc25, YopH, mPTPA and mPTPB.

[1]  Jia Li,et al.  Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase 1B inhibitors , 2013, Journal of enzyme inhibition and medicinal chemistry.

[2]  Zhon-Yin Zhang,et al.  Bicyclic benzofuran and indole-based salicylic acids as protein tyrosine phosphatase inhibitors. , 2012, Bioorganic & medicinal chemistry.

[3]  T. Mustelin,et al.  Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation , 2012, ACS chemical biology.

[4]  B. Lie,et al.  LYP inhibits T cell activation when dissociated from CSK , 2012, Nature chemical biology.

[5]  V. Goldfarb,et al.  Small molecule receptor protein tyrosine phosphatase γ (RPTPγ) ligands that inhibit phosphatase activity via perturbation of the tryptophan-proline-aspartate (WPD) loop. , 2011, Journal of medicinal chemistry.

[6]  Zhon-Yin Zhang,et al.  Small molecule inhibitors of SHP2 tyrosine phosphatase discovered by virtual screening. , 2011, Bioorganic & medicinal chemistry letters.

[7]  M. Sodeoka,et al.  Development of a Vaccinia H1‐Related (VHR) Phosphatase Inhibitor with a Nonacidic Phosphate‐Mimicking Core Structure , 2011, ChemMedChem.

[8]  D. Waugh,et al.  Utilization of nitrophenylphosphates and oxime-based ligation for the development of nanomolar affinity inhibitors of the Yersinia pestis outer protein H (YopH) phosphatase. , 2011, Journal of medicinal chemistry.

[9]  Nunzio Bottini,et al.  Discovery of a novel series of inhibitors of lymphoid tyrosine phosphatase with activity in human T cells. , 2011, Journal of medicinal chemistry.

[10]  T. Mustelin,et al.  Inhibition of the Hematopoietic Protein Tyrosine Phosphatase by Phenoxyacetic Acids. , 2011, ACS medicinal chemistry letters.

[11]  B. Shen,et al.  SHP2 is a target of the immunosuppressant tautomycetin. , 2011, Chemistry & biology.

[12]  Yuehong Wang,et al.  Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from Mycobacterium tuberculosis. , 2010, ACS medicinal chemistry letters.

[13]  A. Barr.  Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development. , 2010, Future medicinal chemistry.

[14]  Abraham Thomas,et al.  Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents. , 2010, European journal of medicinal chemistry.

[15]  Jie Wu,et al.  Targeting protein tyrosine phosphatases for anticancer drug discovery. , 2010, Current pharmaceutical design.

[16]  H. Morinaga,et al.  Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT‐551 , 2010, Diabetes, obesity & metabolism.

[17]  A. Combs.  Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer. , 2010, Journal of medicinal chemistry.

[18]  R. Chan,et al.  Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). , 2010, Journal of medicinal chemistry.

[19]  L. Lessard,et al.  The two faces of PTP1B in cancer. , 2010, Biochimica et biophysica acta.

[20]  Yuehong Wang,et al.  Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents , 2010, Proceedings of the National Academy of Sciences.

[21]  P. T. Lang,et al.  Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. , 2009, Bioorganic & medicinal chemistry letters.

[22]  Stefan Vasile,et al.  Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells. , 2009, Journal of medicinal chemistry.

[23]  N. Bottini,et al.  Identifying potent, selective protein tyrosine phosphatase inhibitors from a library of Au(I) complexes. , 2009, Journal of medicinal chemistry.

[24]  Karunakaran A Kalesh,et al.  High-throughput discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitors using click chemistry. , 2009, Organic letters.

[25]  D. Lawrence,et al.  Acquisition of a potent and selective TC-PTP inhibitor via a stepwise fluorophore-tagged combinatorial synthesis and screening strategy. , 2009, Journal of the American Chemical Society.

[26]  Nathanael Gray,et al.  Factors underlying sensitivity of cancers to small-molecule kinase inhibitors , 2009, Nature Reviews Drug Discovery.

[27]  Ivet Bahar,et al.  Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages , 2009, Nature chemical biology.

[28]  M. Blaskovich.  Drug discovery and protein tyrosine phosphatases. , 2009, Current medicinal chemistry.

[29]  D. Vestweber,et al.  VE-PTP controls blood vessel development by balancing Tie-2 activity , 2009, The Journal of cell biology.

[30]  Gang Liu,et al.  Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages. , 2009, The Journal of antimicrobial chemotherapy.

[31]  M. Shipp,et al.  GLEPP1/Protein-tyrosine Phosphatase ϕ Inhibitors Block Chemotaxis in Vitro and in Vivo and Improve Murine Ulcerative Colitis , 2009, Journal of Biological Chemistry.

[32]  T. Hunter.  Tyrosine phosphorylation: thirty years and counting. , 2009, Current opinion in cell biology.

[33]  Peter J Hume,et al.  The Salmonella Effector SptP Dephosphorylates Host AAA+ ATPase VCP to Promote Development of its Intracellular Replicative Niche , 2009, Cell host & microbe.

[34]  Lutz Tautz,et al.  In Silico Screening for PTPN22 Inhibitors: Active Hits from an Inactive Phosphatase Conformation , 2009, ChemMedChem.

[35]  Wen Hwa Lee,et al.  Large-Scale Structural Analysis of the Classical Human Protein Tyrosine Phosphatome , 2009, Cell.

[36]  W. Guida,et al.  Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. , 2008, Journal of medicinal chemistry.

[37]  Jörg Rademann,et al.  Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking , 2008, Proceedings of the National Academy of Sciences.

[38]  S. Keyse,et al.  Dual-specificity MAP kinase phosphatases (MKPs) and cancer , 2008, Cancer and Metastasis Reviews.

[39]  Andy Hudmon,et al.  Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases , 2007, Proceedings of the National Academy of Sciences.

[40]  Harald Schwalbe,et al.  Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS). , 2007, Chemistry, an Asian journal.

[41]  I. Bahar,et al.  Structurally Unique Inhibitors of Human Mitogen-Activated Protein Kinase Phosphatase-1 Identified in a Pyrrole Carboxamide Library , 2007, Journal of Pharmacology and Experimental Therapeutics.

[42]  T. Alber,et al.  Fragment-based substrate activity screening method for the identification of potent inhibitors of the Mycobacterium tuberculosis phosphatase PtpB. , 2007, Journal of the American Chemical Society.

[43]  J. Rudolph.  Cdc25 phosphatases: structure, specificity, and mechanism. , 2007, Biochemistry.

[44]  A. Murphy,et al.  Vascular endothelial tyrosine phosphatase (VE-PTP)-null mice undergo vasculogenesis but die embryonically because of defects in angiogenesis , 2007, Proceedings of the National Academy of Sciences.

[45]  A. Bennett,et al.  Protein tyrosine phosphatase function: the substrate perspective. , 2007, The Biochemical journal.

[46]  Zhon-Yin Zhang,et al.  Synthesis and cell-based activity of a potent and selective protein tyrosine phosphatase 1B inhibitor prodrug. , 2007, Journal of medicinal chemistry.

[47]  K. Amarasinghe.  Design and Synthesis of Potent, Non‐Peptidic Inhibitors of HPTPβ. , 2006 .

[48]  N. Tonks,et al.  Protein tyrosine phosphatases: from genes, to function, to disease , 2006, Nature Reviews Molecular Cell Biology.

[49]  D. Vestweber,et al.  Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development. , 2006, Blood.

[50]  M. Tremblay,et al.  PTP1B and TC-PTP: novel roles in immune-cell signaling. , 2006, Canadian journal of physiology and pharmacology.

[51]  Gina S. Gerwe,et al.  Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta. , 2006, Bioorganic & medicinal chemistry letters.

[52]  W. Guida,et al.  Discovery of a Novel Shp2 Protein Tyrosine Phosphatase Inhibitor , 2006, Molecular Pharmacology.

[53]  N. Bottini,et al.  Role of PTPN22 in type 1 diabetes and other autoimmune diseases. , 2006, Seminars in immunology.

[54]  ゲルバー，パトリック,et al.  Glepp-1 inhibitors in the treatment of autoimmune and / or inflammatory diseases , 2006 .

[55]  Herbert Waldmann,et al.  Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. Buxbaum,et al.  Receptor Protein Tyrosine Phosphatase γ Is a Marker for Pyramidal Cells and Sensory Neurons in the Nervous System and Is Not Necessary for Normal Development , 2006, Molecular and Cellular Biology.

[57]  M. Bower,et al.  Potent benzimidazole sulfonamide protein tyrosine phosphatase 1B inhibitors containing the heterocyclic (S)-isothiazolidinone phosphotyrosine mimetic. , 2006, Journal of medicinal chemistry.

[58]  Fabio Cerignoli,et al.  Loss of the VHR dual-specific phosphatase causescell-cycle arrest and senescence , 2006, Nature Cell Biology.

[59]  C. Hellberg,et al.  Protein-tyrosine phosphatases and cancer , 2006, Nature Reviews Cancer.

[60]  A. Nebreda,et al.  Protein kinases and phosphatases as therapeutic targets in cancer , 2006, Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico.

[61]  J. Jais,et al.  Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis , 2006, Annals of neurology.

[62]  Steven J. Schrodi,et al.  PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. , 2005, American journal of human genetics.

[63]  Amit Singh,et al.  Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis. , 2005, Tuberculosis.

[64]  A. Bardelli,et al.  Genetic analysis of the kinome and phosphatome in cancer , 2005, Cellular and Molecular Life Sciences CMLS.

[65]  Brent R Stockwell,et al.  Advances in chemical genetics. , 2005, Annual review of genomics and human genetics.

[66]  Daniela S Krause,et al.  Tyrosine kinases as targets for cancer therapy. , 2005, The New England journal of medicine.

[67]  D. Lawrence,et al.  Design, construction, and intracellular activation of an intramolecularly self-silenced signal transduction inhibitor. , 2005, Angewandte Chemie.

[68]  Andreas Vogt,et al.  The Benzo[c]phenanthridine Alkaloid, Sanguinarine, Is a Selective, Cell-active Inhibitor of Mitogen-activated Protein Kinase Phosphatase-1* , 2005, Journal of Biological Chemistry.

[69]  J. Bixby,et al.  Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development , 2005, The Journal of Neuroscience.

[70]  M. Tremblay,et al.  Selective regulation of tumor necrosis factor–induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase , 2005, Nature Immunology.

[71]  John D. Minna,et al.  Activating Mutations of the Noonan Syndrome-Associated SHP2/PTPN11 Gene in Human Solid Tumors and Adult Acute Myelogenous Leukemia , 2004, Cancer Research.

[72]  F. Pixley,et al.  CSF-1 regulation of the wandering macrophage: complexity in action. , 2004, Trends in cell biology.

[73]  R. Quinton,et al.  The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease. , 2004, The Journal of clinical endocrinology and metabolism.

[74]  Adrian Vella,et al.  Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. , 2004, Diabetes.

[75]  C. Morrison,et al.  Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Kristin G Ardlie,et al.  Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. , 2004, American journal of human genetics.

[77]  Stefan Vasile,et al.  The oxidative mechanism of action of ortho-quinone inhibitors of protein-tyrosine phosphatase alpha is mediated by hydrogen peroxide. , 2004, Archives of biochemistry and biophysics.

[78]  Steven J. Schrodi,et al.  A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. , 2004, American journal of human genetics.

[79]  Joanna M. Sasin,et al.  Protein Tyrosine Phosphatases in the Human Genome , 2004, Cell.

[80]  M. J. Newman,et al.  Structure-based Design of Selective and Potent Inhibitors of Protein-tyrosine Phosphatase β* , 2004, Journal of Biological Chemistry.

[81]  M. Gresser,et al.  Catalytic inactivation of protein tyrosine phosphatase CD45 and protein tyrosine phosphatase 1B by polyaromatic quinones. , 2004, Biochemistry.

[82]  M. Tremblay,et al.  Beyond the Metabolic Function of PTP1B , 2004, Cell cycle.

[83]  Nunzio Bottini,et al.  A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes , 2004, Nature Genetics.

[84]  A. Ullrich,et al.  Interplay between mycobacteria and host signalling pathways , 2004, Nature Reviews Microbiology.

[85]  C. Bayly,et al.  Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[86]  J. Weigelt,et al.  Mechanism of action of pyridazine analogues on protein tyrosine phosphatase 1B (PTP1B). , 2004, Bioorganic & medicinal chemistry letters.

[87]  K. Guertin.  Identification of a Novel Class of Orally Active Pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-Based Hypoglycemic Agents with Protein Tyrosine Phosphatase Inhibitory Activity , 2003 .

[88]  D. Lawrence,et al.  Cellular effects of small molecule PTP1B inhibitors on insulin signaling. , 2003, Biochemistry.

[89]  Ramandeep Singh,et al.  Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs , 2003, Molecular microbiology.

[90]  A. Alonso,et al.  Aurintricarboxylic Acid Blocks in Vitro and in Vivo Activity of YopH, an Essential Virulent Factor of Yersinia pestis, the Agent of Plague* , 2003, Journal of Biological Chemistry.

[91]  L. Setti,et al.  Identification of a novel class of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents with protein tyrosine phosphatase inhibitory activity. , 2003, Bioorganic & medicinal chemistry letters.

[92]  R. Bataille,et al.  A cellular model for myeloma cell growth and maturation based on an intraclonal CD45 hierarchy , 2003, Immunological reviews.

[93]  N. Tonks.  PTP1B: From the sidelines to the front lines! , 2003, FEBS letters.

[94]  J. Licht,et al.  Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia , 2003, Nature Genetics.

[95]  B. Neel,et al.  The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. , 2003, Trends in biochemical sciences.

[96]  A. Fedorov,et al.  Crystal Structure of PTP1B Complexed with a Potent and Selective Bidentate Inhibitor* , 2003, The Journal of Biological Chemistry.

[97]  N. Tonks,et al.  Regulation of Insulin Receptor Signaling by the Protein Tyrosine Phosphatase TCPTP , 2003, Molecular and Cellular Biology.

[98]  J. Denu,et al.  Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal kinase (JNK) , 2002, Oncogene.

[99]  Peter Wipf,et al.  Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors. , 2002, Molecular pharmacology.

[100]  M. Tremblay,et al.  The T Cell Protein Tyrosine Phosphatase Is a Negative Regulator of Janus Family Kinases 1 and 3 , 2002, Current Biology.

[101]  H. Waldmann,et al.  Natural products are biologically validated starting points in structural space for compound library development: solid-phase synthesis of dysidiolide-derived phosphatase inhibitors. , 2002, Angewandte Chemie.

[102]  D. Lawrence,et al.  Acquisition of a Specific and Potent PTP1B Inhibitor from a Novel Combinatorial Library and Screening Procedure* , 2001, The Journal of Biological Chemistry.

[103]  T. Hamaguchi,et al.  TU-572, a Potent and Selective CD45 Inhibitor, Suppresses IgE-Mediated Anaphylaxis and Murine Contact Hypersensitivity Reactions , 2001, International Archives of Allergy and Immunology.

[104]  Michael A. Patton,et al.  Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome , 2001, Nature Genetics.

[105]  Z. Zhang,et al.  Protein tyrosine phosphatases: prospects for therapeutics. , 2001, Current opinion in chemical biology.

[106]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[107]  S. Suchard,et al.  Potent reversible inhibitors of the protein tyrosine phosphatase CD45. , 2001, Journal of medicinal chemistry.

[108]  B. Neel,et al.  Combinatorial control of the specificity of protein tyrosine phosphatases. , 2001, Current opinion in cell biology.

[109]  T. Hamaguchi,et al.  Synthesis and characterization of a potent and selective protein tyrosine phosphatase inhibitor, 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]benzimidazole , 2000 .

[110]  Bernhard Hemmer,et al.  A point mutation in PTPRC is associated with the development of multiple sclerosis , 2000, Nature Genetics.

[111]  M. Mullan,et al.  CD45 Opposes β-Amyloid Peptide-Induced Microglial Activation via Inhibition of p44/42 Mitogen-Activated Protein Kinase , 2000, The Journal of Neuroscience.

[112]  Young-Bum Kim,et al.  Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice , 2000, Molecular and Cellular Biology.

[113]  G. Powis,et al.  Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase. , 2000, Bioorganic & medicinal chemistry.

[114]  T. Mustelin,et al.  Inhibition of T Cell Signaling by Mitogen-activated Protein Kinase-targeted Hematopoietic Tyrosine Phosphatase (HePTP)* , 1999, The Journal of Biological Chemistry.

[115]  B. Kennedy,et al.  Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. , 1999, Science.

[116]  N. Tonks,et al.  Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase , 1998, Molecular and Cellular Biology.

[117]  S. Shoelson,et al.  Crystal Structure of the Tyrosine Phosphatase SHP-2 , 1998, Cell.

[118]  D S Lawrence,et al.  Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[119]  J. Siekierka,et al.  Nitroarylhydroxymethylphosphonic acids as inhibitors of CD45. , 1997, Bioorganic & medicinal chemistry.

[120]  John Wagner,et al.  Impaired Bone Marrow Microenvironment and Immune Function in T Cell Protein Tyrosine Phosphatase–deficient Mice , 1997, The Journal of experimental medicine.

[121]  J. Bliska,et al.  Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions , 1997, The EMBO journal.

[122]  M. Loda,et al.  CDC25 phosphatases as potential human oncogenes. , 1995, Science.

[123]  H. Griesser,et al.  A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1. , 1994, Leukemia.

[124]  M. Minden,et al.  Cloning and expression of an inducible lymphoid‐specific, protein tyrosine phosphatase (HePTPase) , 1992, European journal of immunology.

[125]  P. Nowell,et al.  Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[126]  D. Hart,et al.  Anti-leucocyte common (CD45) antibodies inhibit dendritic cell stimulation of CD4 and CD8 T-lymphocyte proliferation. , 1990, Immunology.

[127]  Matthew L. Thomas,et al.  Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation , 1989, Cell.

[128]  M. Doddareddy,et al.  Targeting mitogen-activated protein kinase phosphatase-1 (MKP-1): structure-based design of MKP-1 inhibitors and upregulators. , 2012, Current medicinal chemistry.

[129]  S. Hardy,et al.  Inside the human cancer tyrosine phosphatome , 2010, Nature Reviews Cancer.

[130]  Steven J. Schrodi,et al.  Genetic Variation : Evidence for Multiple Variants Associated with Rheumatoid Arthritis , 2005 .

[131]  Zhon-Yin Zhang.  Mechanistic studies on protein tyrosine phosphatases. , 2003, Progress in nucleic acid research and molecular biology.

[132]  Zhon-Yin Zhang,et al.  Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development. , 2002, Annual review of pharmacology and toxicology.

[133]  Y. Wu,et al.  CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase. , 2000, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[134]  N. Tonks,et al.  Epidermal Growth Factor Receptor and the Adaptor Protein p 52 Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase , 1998 .