protein tyrosine phosphatases


Summary: An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.

Top Publications

  1. Kantoff P, Higano C, Small E, Whitmore J, Frohlich M, Schellhammer P. Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst. 2012;104:1107-9; author reply 1109-12 pubmed publisher
  2. Sawai M, Uchida Y, Ohno Y, Miyamoto M, Nishioka C, Itohara S, et al. The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways. J Biol Chem. 2017;292:15538-15551 pubmed publisher
    ..Our findings are important for furthering the understanding of the molecular mechanisms in FA elongation and diversity. ..
  3. Frankson R, Yu Z, Bai Y, Li Q, Zhang R, Zhang Z. Therapeutic Targeting of Oncogenic Tyrosine Phosphatases. Cancer Res. 2017;77:5701-5705 pubmed publisher
    b>Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis...
  4. Luo M, Flood E, Almeida D, Yan L, Berlin D, Heerdt P, et al. Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases. J Exp Med. 2017;214:2535-2545 pubmed publisher
    ..We conclude that ANXA2 contributes to pulmonary microvascular integrity by enabling VEC-related phosphatase activity, thereby preventing vascular leak during alveolar hypoxia. ..
  5. Riddiford N, Schlosser G. Six1 and Eya1 both promote and arrest neuronal differentiation by activating multiple Notch pathway genes. Dev Biol. 2017;431:152-167 pubmed publisher
  6. Ono R, Masuya M, Ishii S, Katayama N, Nosaka T. Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced Leukemogenesis. Mol Cell Biol. 2017;37: pubmed publisher
    ..Therefore, EYA2 may be a target for molecular therapy in this subtype of AML, including PLZF-RARA APL. ..
  7. Pulido R, Stoker A, Hendriks W. PTPs emerge as PIPs: protein tyrosine phosphatases with lipid-phosphatase activities in human disease. Hum Mol Genet. 2013;22:R66-76 pubmed publisher
    b>Protein tyrosine phosphatases (PTPs) constitute a family of key homeostatic regulators, with wide implications on physiology and disease...
  8. Drake C. Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst. 2012;104:1422; author reply 1422-3 pubmed
  9. Pei J, Gong C, Iqbal K, Grundke Iqbal I, Wu Q, Winblad B, et al. Subcellular distribution of protein phosphatases and abnormally phosphorylated tau in the temporal cortex from Alzheimer's disease and control brains. J Neural Transm (Vienna). 1998;105:69-83 pubmed

More Information


  1. Nakahara Y, Nagai H, Kinoshita T, Uchida T, Hatano S, Murate T, et al. Mutational analysis of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma. Leukemia. 1998;12:1277-80 pubmed
    ..These findings suggest that alterations in the PTEN/MMAC1 gene play a role in the pathogenesis of NHL. ..
  2. van der Meulen T, Swarts S, Fischer W, van der Geer P. Identification of STS-1 as a novel ShcA-binding protein. Biochem Biophys Res Commun. 2017;490:1334-1339 pubmed publisher
    ..Our results further show that the interaction between STS-1 and ShcA is regulated in response to EGF receptor activation. ..
  3. Klingbeil K, Greenland C, Arslan S, Llamos Paneque A, Gurkan H, Demir Ulusal S, et al. Novel EYA1 variants causing Branchio-oto-renal syndrome. Int J Pediatr Otorhinolaryngol. 2017;98:59-63 pubmed publisher
    ..A variety of DNA changes including large deletions underlie BOR syndrome in different populations, which can be detected with comprehensive genetic testing. ..
  4. Machado L, Shen T, Page R, Peti W. The KIM-family protein-tyrosine phosphatases use distinct reversible oxidation intermediates: Intramolecular or intermolecular disulfide bond formation. J Biol Chem. 2017;292:8786-8796 pubmed publisher
    ..In summary, despite being closely related, KIM-PTPs significantly differ in oxidation profiles. These findings highlight that oxidation protection is critical when analyzing PTPs, for example, in drug screening. ..
  5. Gulley J, Leitman S, Dahut W, Schlom J. Re: interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer. J Natl Cancer Inst. 2012;104:1106; author reply 1109-12 pubmed publisher
  6. Grønbaek K, Zeuthen J, Guldberg P, Ralfkiaer E, Hou Jensen K. Alterations of the MMAC1/PTEN gene in lymphoid malignancies. Blood. 1998;91:4388-90 pubmed
  7. Lou Z, Jevremovic D, Billadeau D, Leibson P. A balance between positive and negative signals in cytotoxic lymphocytes regulates the polarization of lipid rafts during the development of cell-mediated killing. J Exp Med. 2000;191:347-54 pubmed
    ..These results suggest that the influence of integrated positive and negative signals on raft redistribution critically influences the development of cell-mediated cytotoxicity. ..
  8. Qi Y, Gao F, Hou L, Wan C. Anti-Inflammatory and Immunostimulatory Activities of Astragalosides. Am J Chin Med. 2017;45:1157-1167 pubmed publisher
    ..These pharmacological properties highlight the traditional uses of Astragalus and provide a new direction for subsequent research and the clinical application of this traditional herbal. ..
  9. Masliah E, Mallory M, Hansen L, Alford M, Albright T, Terry R, et al. Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in Alzheimer's disease. Acta Neuropathol. 1991;83:12-20 pubmed
    ..The presence of the anti-CD45 immunoreactivity in microglia suggests the possibility that they may require the presence of CD45 as a cell surface receptor which may regulate cell function through modulation of intracellular signaling. ..
  10. Drake C. Immunotherapy for prostate cancer: walk, don't run. J Clin Oncol. 2009;27:4035-7 pubmed publisher
  11. Kohno T, Takahashi M, Manda R, Yokota J. Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes Chromosomes Cancer. 1998;22:152-6 pubmed
    ..All the lung tumors with PTEN/MMAC1/TEP1 mutations were homozygous for the mutant alleles. These findings suggest that PTEN/MMAC1/TEP1 plays a role as a tumor suppressor gene in the genesis and/or progression of human lung cancer. ..
  12. Leitherer S, Clos J, Liebler Tenorio E, Schleicher U, Bogdan C, Soulat D. Characterization of the Protein Tyrosine Phosphatase LmPRL-1 Secreted by Leishmania major via the Exosome Pathway. Infect Immun. 2017;85: pubmed publisher
    ..major led to an increased number of parasites in macrophages. From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracellular survival of the parasites in macrophages. ..
  13. Castro Sánchez P, Ramirez Munoz R, Roda Navarro P. Gene Expression Profiles of Human Phosphotyrosine Phosphatases Consequent to Th1 Polarisation and Effector Function. J Immunol Res. 2017;2017:8701042 pubmed publisher
    ..We expect that those PTPs that regulate T helper polarisation will constitute potential targets for intervening CD4 T cell immune responses in order to generate new therapies for the treatment of autoimmune diseases. ..
  14. Pinotsis N, Waksman G. Structure of the WipA protein reveals a novel tyrosine protein phosphatase effector from Legionella pneumophila. J Biol Chem. 2017;292:9240-9251 pubmed publisher
    ..In conclusion, these findings help advance our understanding of the molecular mechanisms of an effector involved in Legionella virulence and may inform approaches to elucidate the function of other effectors. ..
  15. Kobayashi J, Matsuura Y. Structure and dimerization of the catalytic domain of the protein phosphatase Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae. Protein Sci. 2017;26:2105-2112 pubmed publisher
    ..The dimerization interface is located on the backside of the substrate-binding cleft. Structure-based mutational analyses indicate that the dimerization of Cdc14p is required for normal growth of yeast cells. ..
  16. Guan K, Dixon J. Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal Biochem. 1991;192:262-7 pubmed
    ..The vector, pGEX-KG, has also been modified to facilitate cloning of a variety of cDNAs in all reading frames and has been successfully used to express several eukaryotic proteins. ..
  17. Hale A, Ter Steege E, den Hertog J. Recent advances in understanding the role of protein-tyrosine phosphatases in development and disease. Dev Biol. 2017;428:283-292 pubmed publisher
    ..The tentative importance of PTPs in these processes is highlighted by the diseases that present upon aberrant activity. ..
  18. Levine E, Dreyfus C, Black I, Plummer M. Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors. Proc Natl Acad Sci U S A. 1995;92:8074-7 pubmed
    ..These results suggest a role for BDNF in the modulation of synaptic transmission in the hippocampus. ..
  19. Tashiro H, Blazes M, Wu R, Cho K, Bose S, Wang S, et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res. 1997;57:3935-40 pubmed
    ..Our results support PTEN as a tumor suppressor gene and suggest that mutations in PTEN play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. ..
  20. Paillusson S, Gomez Suaga P, Stoica R, LITTLE D, Gissen P, Devine M, et al. α-Synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production. Acta Neuropathol. 2017;134:129-149 pubmed publisher
    ..Such disruptions are likely to be particularly damaging to neurons that are heavily dependent on correct Ca2+ signaling and ATP. ..
  21. Dhanjal J, Grover S, Sharma S, Singh A, Grover A. Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors. BMC Genomics. 2014;15 Suppl 1:S3 pubmed publisher
    ..These inhibitors have the potential to evolve as lead molecules in the development of drugs for the treatment of tuberculosis. ..
  22. Mandell J, Banker G. Selective blockade of axonogenesis in cultured hippocampal neurons by the tyrosine phosphatase inhibitor orthovanadate. J Neurobiol. 1998;35:17-28 pubmed
    ..These data suggest a potentially important role for tyrosine phosphatases and their phosphoprotein substrates in axonogenesis. ..
  23. Liang X, Sun H, Shen W, Wang S, Yao J, Migawa M, et al. Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels. Nucleic Acids Res. 2017;45:9528-9546 pubmed publisher
    ..Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. ..
  24. Goodin K, Prucka S, Woolley A, Kohlhase J, Smith R, Grant J, et al. Familial transmission of oculoauriculovertebral spectrum (Goldenhar syndrome) is not due to mutations in either EYA1 or SALL1. Am J Med Genet A. 2009;149A:535-8 pubmed publisher
  25. Lee J, Shi Y, Vega M, Yang Y, Gera J, Jung M, et al. Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction. Bioorg Med Chem Lett. 2017;27:4714-4724 pubmed publisher
    ..Due to their targeting of DEPTOR, these compounds activate mTORC1 and selectively induce MM cell apoptosis and cell cycle arrest. ..
  26. Lioger B, Rollin J, Vayne C, Perret Gallix K, Pouplard C, Godeau B, et al. No impact of PTPN22, PTPRJ and ACP1 genes polymorphisms on the risk of immune thrombocytopenia in French adult patients. Thromb Res. 2016;144:76-8 pubmed publisher
  27. Chan K, Alonso Nuñez M, Grallert A, Tanaka K, Connolly Y, Smith D, et al. Dialogue between centrosomal entrance and exit scaffold pathways regulates mitotic commitment. J Cell Biol. 2017;216:2795-2812 pubmed publisher
    ..Such integration of signals emanating from neighboring scaffolds shows how centrosomes/SPBs can integrate inputs from multiple pathways to control cell fate. ..
  28. Chen X, Wang J, Mitchell E, Guo J, Wang L, Zhang Y, et al. Recurrent 8q13.2-13.3 microdeletions associated with branchio-oto-renal syndrome are mediated by human endogenous retroviral (HERV) sequence blocks. BMC Med Genet. 2014;15:90 pubmed publisher
    ..These findings raise the potential that HERV sequences may more commonly underlie recombination of dosage sensitive regions associated with recurrent syndromes. ..
  29. Wang S, Parsons R, Ittmann M. Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas. Clin Cancer Res. 1998;4:811-5 pubmed
    ..No small mutations within PTEN exons were found in any tumors exhibiting alterations on 10q23. Thus, inactivation of the PTEN gene by homozygous deletion occurs in approximately 10-15% of primary stage B prostate carcinomas. ..
  30. Stanford S, Bottini N. Targeting Tyrosine Phosphatases: Time to End the Stigma. Trends Pharmacol Sci. 2017;38:524-540 pubmed publisher
    b>Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, and several PTPs have been validated as therapeutic targets for human diseases...
  31. Rollin J, Pouplard C, Leroux D, May M, Gruel Y. Impact of polymorphisms affecting the ACP1 gene on levels of antibodies against platelet factor 4-heparin complexes. J Thromb Haemost. 2013;11:1609-11 pubmed publisher
  32. Chan W, Knowlton G, Bishop A. Activation of Engineered Protein Tyrosine Phosphatases with the Biarsenical Compound AsCy3-EDT2. Chembiochem. 2017;18:1950-1958 pubmed publisher
    ..Here we present a strategy for engineering chemically activatable protein tyrosine phosphatases (actPTPs). To generate actPTP1B, we introduced three cysteine point mutations in the enzyme's WPD loop...
  33. Yip S, Crew A, Gee J, Hui R, Blamey R, Robertson J, et al. Up-regulation of the protein tyrosine phosphatase SHP-1 in human breast cancer and correlation with GRB2 expression. Int J Cancer. 2000;88:363-8 pubmed
    ..Since these proteins can bind to each other and regulate MEK/MAP kinase activation, their co-ordinate up-regulation may amplify tyrosine kinase signaling in breast cancer cells. ..
  34. Segovia D, Haouz A, Porley D, Olivero N, Martinez M, Mariadassou M, et al. OH1 from Orf Virus: A New Tyrosine Phosphatase that Displays Distinct Structural Features and Triple Substrate Specificity. J Mol Biol. 2017;429:2816-2824 pubmed publisher
  35. Von Stetina J, Frawley L, Unhavaithaya Y, Orr Weaver T. Variant cell cycles regulated by Notch signaling control cell size and ensure a functional blood-brain barrier. Development. 2018;145: pubmed publisher
    ..Decreased Notch signaling promotes endomitosis even in the ventral nerve cord SPG that normally are mononucleate, but not in the endocycling salivary gland cells, revealing tissue-specific cell cycle responses. ..
  36. Stoker A, Gehrig B, Haj F, Bay B. Axonal localisation of the CAM-like tyrosine phosphatase CRYP alpha: a signalling molecule of embryonic growth cones. Development. 1995;121:1833-44 pubmed
    ..Here we present the first evidence that vertebrate cell adhesion molecule-like protein tyrosine phosphatases are likely to be components of this signalling system...
  37. Takahashi K, Kim R, Lauhan C, Park Y, Nguyen N, Vestweber D, et al. Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature. PLoS ONE. 2017;12:e0177192 pubmed publisher
  38. Nguyen D, Seo U, Zhao B, Le D, Seong S, Choi J, et al. Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities. Bioorg Chem. 2017;72:293-300 pubmed publisher
    ..Most of them were found to have moderate inhibitory effects, with IC50 values ranging from 60.20±1.09 to 92.85±1.12?M. Except compounds 3, 8, and 18 were inactive. ..
  39. Li T, Xu X, Li J, Xing S, Zhang L, Li W, et al. Association of ACP1 gene polymorphisms and coronary artery disease in northeast Chinese population. J Genet. 2015;94:125-8 pubmed
  40. Georgescu M, Yell P, Mobley B, Shang P, Georgescu T, Wang S, et al. NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma. Acta Neuropathol Commun. 2015;3:11 pubmed publisher
    ..These data highlight a role for NHERF1 in ependymal morphogenesis with direct application to the diagnosis of ependymal tumors. ..
  41. Bhalla U, Iyengar R. Emergent properties of networks of biological signaling pathways. Science. 1999;283:381-7 pubmed
    ..These properties of signaling networks raise the possibility that information for "learned behavior" of biological systems may be stored within intracellular biochemical reactions that comprise signaling pathways. ..
  42. Kim J, Cho H, Ryu S, Choi M. Effects of metal ions on the activity of protein tyrosine phosphatase VHR: highly potent and reversible oxidative inactivation by Cu2+ ion. Arch Biochem Biophys. 2000;382:72-80 pubmed
    The posttranslational regulation of protein tyrosine phosphatases (PTPs) has been suggested to have a crucial role in maintaining the phosphotyrosine level in cells...
  43. Davicino R, Méndez Huergo S, Eliçabe R, Stupirski J, Autenrieth I, Di Genaro M, et al. Galectin-1-Driven Tolerogenic Programs Aggravate Yersinia enterocolitica Infection by Repressing Antibacterial Immunity. J Immunol. 2017;199:1382-1392 pubmed publisher
    ..enterocolitica infection. Thus, targeting Gal-1-glycan interactions may contribute to reinforce antibacterial responses by reprogramming innate and adaptive immune mechanisms. ..
  44. Graves J, Campbell J, Krebs E. Protein serine/threonine kinases of the MAPK cascade. Ann N Y Acad Sci. 1995;766:320-43 pubmed
  45. Lee S, Kwon K, Kim S, Rhee S. Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem. 1998;273:15366-72 pubmed
  46. Kurose K, Bando K, Fukino K, Sugisaki Y, Araki T, Emi M. Somatic mutations of the PTEN/MMAC1 gene in fifteen Japanese endometrial cancers: evidence for inactivation of both alleles. Jpn J Cancer Res. 1998;89:842-8 pubmed
  47. Bruder L, Gruninger R, Cleland C, Mosimann S. Bacterial PhyA protein-tyrosine phosphatase-like myo-inositol phosphatases in complex with the Ins(1,3,4,5)P4 and Ins(1,4,5)P3 second messengers. J Biol Chem. 2017;292:17302-17311 pubmed publisher
  48. Sun H, Tan L, Gao L, Yao S. High-throughput screening of catalytically inactive mutants of protein tyrosine phosphatases (PTPs) in a phosphopeptide microarray. Chem Commun (Camb). 2009;:677-9 pubmed publisher
    ..a novel phosphopeptide microarray capable of noncovalently "trapping" catalytically inactive mutants of protein tyrosine phosphatases (PTPs), and its application in high-throughput determination of PTP substrate specificity.
  49. Zhou W, Yin Y, Weinheimer A, Kaur N, Carpino N, French J. Structural and Functional Characterization of the Histidine Phosphatase Domains of Human Sts-1 and Sts-2. Biochemistry. 2017;56:4637-4645 pubmed publisher
    ..Collectively, these data suggest that the human Sts proteins are druggable targets and provide a structural basis for future drug development efforts...
  50. Sallorenzo C, Silva R, Kasamatsu T, Dib S. Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance. Arch Endocrinol Metab. 2017;61:361-366 pubmed publisher
    ..However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases. ..
  51. Parashar K, Kopping E, Frank D, Sampath V, Thanassi D, Carpino N. Increased Resistance to Intradermal Francisella tularensis LVS Infection by Inactivation of the Sts Phosphatases. Infect Immun. 2017;85: pubmed publisher
    ..These observations suggest the Sts proteins play an important regulatory role in the host response to bacterial infection, and they underscore a role for Sts in regulating functionally relevant immune response pathways. ..
  52. Fisher G, Sachs D, Voorhees J. Ageing: collagenase-mediated collagen fragmentation as a rejuvenation target. Br J Dermatol. 2014;171:446-9 pubmed publisher