PTPN2

Summary

Gene Symbol: PTPN2
Description: protein tyrosine phosphatase, non-receptor type 2
Alias: PTN2, PTPT, TC-PTP, TCELLPTP, TCPTP, tyrosine-protein phosphatase non-receptor type 2, T-cell protein tyrosine phosphatase
Species: human
Products:     PTPN2

Top Publications

  1. Scharl M, Paul G, Weber A, Jung B, Docherty M, Hausmann M, et al. Protection of epithelial barrier function by the Crohn's disease associated gene protein tyrosine phosphatase n2. Gastroenterology. 2009;137:2030-2040.e5 pubmed publisher
    Protein tyrosine phosphatase N2 (PTPN2) has been identified as a Crohn's disease (CD) candidate gene. However, a role for PTPN2 in the pathogenesis of CD has not been identified...
  2. Sangwan V, Paliouras G, Abella J, Dubé N, Monast A, Tremblay M, et al. Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase. J Biol Chem. 2008;283:34374-83 pubmed publisher
    The non-receptor protein-tyrosine phosphatases (PTPs) 1B and T-cell phosphatase (TCPTP) have been implicated as negative regulators of multiple signaling pathways including receptor-tyrosine kinases...
  3. Espino Paisan L, de la Calle H, Fernandez Arquero M, Figueredo M, De la Concha E, Urcelay E, et al. A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes. Immunogenetics. 2011;63:255-8 pubmed publisher
    The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D)...
  4. Moore F, Colli M, Cnop M, Esteve M, Cardozo A, Cunha D, et al. PTPN2, a candidate gene for type 1 diabetes, modulates interferon-gamma-induced pancreatic beta-cell apoptosis. Diabetes. 2009;58:1283-91 pubmed publisher
    ..Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays a direct role in beta-cell demise and assessed PTPN2 expression in human islets ..
  5. Simoncic P, Lee Loy A, Barber D, Tremblay M, McGlade C. The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3. Curr Biol. 2002;12:446-53 pubmed
    ..Mice deficient for the T cell protein tyrosine phosphatase (TCPTP) display gross defects in the hematopoietic compartment, indicating a critical role for ..
  6. Parkes M, Barrett J, Prescott N, Tremelling M, Anderson C, Fisher S, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet. 2007;39:830-2 pubmed
    ..We obtained replication for the autophagy-inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 x 10(-4), combined P = 2.1 x 10(-10)) and for nine other loci, including NKX2-3, PTPN2 and gene deserts on chromosomes 1q and 5p13.
  7. Tiganis T, Flint A, Adam S, Tonks N. Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97. J Biol Chem. 1997;272:21548-57 pubmed
    Alternative splicing of the T-cell protein tyrosine phosphatase (TCPTP) transcript generates two forms of the enzyme that differ at their extreme C termini: a 48-kDa endoplasmic reticulum-associated form and a 45-kDa nuclear form...
  8. ten Hoeve J, de Jesus Ibarra Sanchez M, Fu Y, Zhu W, Tremblay M, David M, et al. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol. 2002;22:5662-8 pubmed
    ..The dephosphorylation of Stat3, but not Stat5 or Stat6, is also affected in TC-PTP-null cells. Our results identify TC45 as a PTP responsible for the dephosphorylation of Stat1 in the nucleus. ..
  9. Zhu W, Mustelin T, David M. Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. J Biol Chem. 2002;277:35787-90 pubmed
    ..the rate of STAT1 dephosphorylation by modulating its interaction with PIAS1 and the nuclear tyrosine phosphatase TcPTP. Inhibition of STAT1 arginine methylation, or mutation of STAT1 Arg-31, results in a prolonged half-life of STAT1 ..

More Information

Publications82

  1. Todd J, Walker N, Cooper J, Smyth D, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39:857-64 pubmed
    ..Several regions, including 18q22 and 18p11, showed association with autoimmune thyroid disease. This study increases the number of T1D loci with compelling evidence from six to at least ten. ..
  2. Santin I, Moore F, Colli M, Gurzov E, Marselli L, Marchetti P, et al. PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic ?-cell apoptosis via regulation of the BH3-only protein Bim. Diabetes. 2011;60:3279-88 pubmed publisher
    ..We presently evaluated the mechanisms by which PTPN2, a candidate gene for T1D, modulates ?-cell apoptosis after exposure to type I and II interferons (IFNs), ..
  3. Persson C, Sävenhed C, Bourdeau A, Tremblay M, Markova B, Bohmer F, et al. Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase. Mol Cell Biol. 2004;24:2190-201 pubmed
    ..In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors. ..
  4. Prahalad S, Hansen S, Whiting A, Guthery S, Clifford B, McNally B, et al. Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2124-30 pubmed publisher
    ..rs3761847 in the TRAF1/C5 locus, rs2104286 in the IL2RA locus, rs7574865 in the STAT4 locus, and rs2542151 in the PTPN2 locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes...
  5. Scharl M, McCole D, Weber A, Vavricka S, Frei P, Kellermeier S, et al. Protein tyrosine phosphatase N2 regulates TNF?-induced signalling and cytokine secretion in human intestinal epithelial cells. Gut. 2011;60:189-97 pubmed publisher
    The Crohn's disease (CD) susceptibility gene, protein tyrosine phosphatase N2 (PTPN2), regulates interferon ? (IFN?)-induced signalling and epithelial barrier function in T?? intestinal epithelial cells (IECs)...
  6. Lu X, Chen J, Sasmono R, Hsi E, Sarosiek K, Tiganis T, et al. T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. Mol Cell Biol. 2007;27:2166-79 pubmed
    ..Among the differentially expressed PTPs, only T-cell PTP (TCPTP) localizes to the nucleus...
  7. Gupta V, Swarup G. Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER. J Cell Sci. 2006;119:1703-14 pubmed
    ..We suggest that TC48 translocates to the Golgi complex along the secretory pathway, whereas its ER localization is maintained by selective retrieval enabled by interactions with p25 and p23. ..
  8. van Vliet C, Bukczynska P, Puryer M, Sadek C, Shields B, Tremblay M, et al. Selective regulation of tumor necrosis factor-induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase. Nat Immunol. 2005;6:253-60 pubmed
    ..b>T cell protein tyrosine phosphatase (TCPTP) is essential for hematopoietic development and negatively regulates inflammatory responses...
  9. Galic S, Hauser C, Kahn B, Haj F, Neel B, Tonks N, et al. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol. 2005;25:819-29 pubmed
    ..Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic, M...
  10. Pasquali C, Curchod M, Walchli S, Espanel X, Guerrier M, Arigoni F, et al. Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor. Mol Endocrinol. 2003;17:2228-39 pubmed
  11. Mattila E, Pellinen T, Nevo J, Vuoriluoto K, Arjonen A, Ivaska J. Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP. Nat Cell Biol. 2005;7:78-85 pubmed
    ..tail of alpha(1) integrin selectively interacts with a ubiquitously expressed protein tyrosine phosphatase TCPTP (T-cell protein tyrosine phosphatase) and activates it after cell adhesion to collagen...
  12. Yamamoto T, Sekine Y, Kashima K, Kubota A, Sato N, Aoki N, et al. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochem Biophys Res Commun. 2002;297:811-7 pubmed
    ..Endogenous TC-PTP complexed with STAT3 in the nucleus of M1 cells. These results strongly suggest that the nuclear isoform of TC-PTP may serve as a negative regulator of IL-6-mediated signaling pathway. ..
  13. Weersma R, Stokkers P, Cleynen I, Wolfkamp S, Henckaerts L, Schreiber S, et al. Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch-Belgian cohort. Am J Gastroenterol. 2009;104:630-8 pubmed publisher
    ..We replicated genetic associations for CD with IL23R, ATG16L1, IRGM, NKX2-3, 1q24, 10q21, 5p13, and PTPN2 and report evidence for associations with HERC2 and CCNY...
  14. Tiganis T, Bennett A, Ravichandran K, Tonks N. Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Mol Cell Biol. 1998;18:1622-34 pubmed
    T-cell protein tyrosine phosphatase (TCPTP) exists as two forms generated by alternative splicing: a 48-kDa endoplasmic reticulum (ER)-associated form (TC48) and a 45-kDa nuclear form (TC45)...
  15. Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, et al. Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. Nat Genet. 2012;44:511-6 pubmed publisher
    ..0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0...
  16. Lorenzen J, Dadabay C, Fischer E. COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. J Cell Biol. 1995;131:631-43 pubmed
    The noncatalytic domain of the human T cell protein tyrosine phosphatase (TCPTP) is alternatively spliced to generate a 45-kD form, p45TC, and a 48-kD form, p48TC (Champion-Arnaud et al., 1991; Mosinger et al., 1992)...
  17. Smyth D, Plagnol V, Walker N, Cooper J, Downes K, Yang J, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767-77 pubmed publisher
    ..81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared ..
  18. Long S, Cerosaletti K, Wan J, Ho J, Tatum M, Wei S, et al. An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4(+) T cells. Genes Immun. 2011;12:116-25 pubmed publisher
    ..One of these, PTPN2, encodes a protein tyrosine phosphatase that is highly expressed in T cells and regulates cytokine signaling...
  19. Morgan A, Han D, Huebner C, Lam W, Fraser A, Ferguson L. PTPN2 but not PTPN22 is associated with Crohn's disease in a New Zealand population. Tissue Antigens. 2010;76:119-25 pubmed publisher
    Recent genome-wide association studies have provided evidence for the involvement of the genes PTPN2 and PTPN22 in the pathogenesis of Crohn's disease (CD)...
  20. Cool D, Tonks N, Charbonneau H, Walsh K, Fischer E, Krebs E. cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. Proc Natl Acad Sci U S A. 1989;86:5257-61 pubmed
    ..In view of the high degree of similarity, the T-cell cDNA likely encodes a newly discovered protein-tyrosine-phosphatase, thus expanding this family of genes. ..
  21. Scharl M, Mwinyi J, Fischbeck A, Leucht K, Eloranta J, Arikkat J, et al. Crohn's disease-associated polymorphism within the PTPN2 gene affects muramyl-dipeptide-induced cytokine secretion and autophagy. Inflamm Bowel Dis. 2012;18:900-12 pubmed publisher
    ..SNP) rs2542151 within the gene locus region encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) has been associated with Crohn's disease (CD), ulcerative colitis (UC), type-I diabetes, and rheumatoid arthritis...
  22. Hinks A, Cobb J, Sudman M, Eyre S, Martin P, Flynn E, et al. Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap. Ann Rheum Dis. 2012;71:1117-21 pubmed publisher
    ..The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
  23. McCole D. Regulation of epithelial barrier function by the inflammatory bowel disease candidate gene, PTPN2. Ann N Y Acad Sci. 2012;1257:108-14 pubmed publisher
    Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) has been identified as an inflammatory bowel disease (IBD) candidate gene...
  24. Mattila E, Auvinen K, Salmi M, Ivaska J. The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling. J Cell Sci. 2008;121:3570-80 pubmed publisher
    ..Here, our objective was to study whether T-cell protein tyrosine phosphatase (TCPTP, also known as PTN2), which we found to be expressed in human endothelial cells, could alter VEGF signalling by ..
  25. Franke A, Balschun T, Karlsen T, Hedderich J, May S, Lu T, et al. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008;40:713-5 pubmed publisher
    ..Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.
  26. Mosinger B, Tillmann U, Westphal H, Tremblay M. Cloning and characterization of a mouse cDNA encoding a cytoplasmic protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1992;89:499-503 pubmed
    ..An additional 1.3-kilobase message was found to be expressed specifically in testes. Finally, we report the isolation of a human T-cell PTP cDNA containing a 3' end sequence homologous to the mouse PTP. ..
  27. Galic S, Klingler Hoffmann M, Fodero Tavoletti M, Puryer M, Meng T, Tonks N, et al. Regulation of insulin receptor signaling by the protein tyrosine phosphatase TCPTP. Mol Cell Biol. 2003;23:2096-108 pubmed
    The human protein tyrosine phosphatase TCPTP exists as two forms: an endoplasmic reticulum-targeted 48-kDa form (TC48) and a nuclear 45-kDa form (TC45)...
  28. Gupta S, Radha V, Sudhakar C, Swarup G. A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis. FEBS Lett. 2002;532:61-6 pubmed
    ..These results suggest that caspase-1 may be one of the mediators of p53-dependent apoptosis in human cells. ..
  29. Shields B, Court N, Hauser C, Bukczynska P, Tiganis T. Cell cycle-dependent regulation of SFK, JAK1 and STAT3 signalling by the protein tyrosine phosphatase TCPTP. Cell Cycle. 2008;7:3405-16 pubmed
    ..Previous studies have established that the protein tyrosine phosphatase TCPTP can dephosphorylate and inactivate the SFK and JAK protein tyrosine kinases (PTKs) to attenuate cytokine ..
  30. Penrose H, MARCHELLETTA R, Krishnan M, McCole D. Spermidine stimulates T cell protein-tyrosine phosphatase-mediated protection of intestinal epithelial barrier function. J Biol Chem. 2013;288:32651-62 pubmed publisher
    ..Expression of the PTPN2 gene product, T cell protein-tyrosine phosphatase (TCPTP), in intestinal epithelial cells has been shown to play an important role in the protection of epithelial barrier ..
  31. Lan X, Zhao C, Chen X, Zhang P, Zang D, Wu J, et al. Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation. Cell Death Dis. 2017;8:e2913 pubmed publisher
    ..We recently reported that platinum pyrithione (PtPT) potently inhibits the ubiquitin-proteasome system (UPS) via targeting the 26 S proteasome-associated ..
  32. Johnson C, Cool D, Glaccum M, Green N, Fischer E, Bruskin A, et al. Isolation and mapping of human T-cell protein tyrosine phosphatase sequences: localization of genes and pseudogenes discriminated using fluorescence hybridization with genomic versus cDNA probes. Genomics. 1993;16:619-29 pubmed
    ..To address this, four genomic clones were obtained with homology to the TC PTP cDNA and characterized for their primary structure and their position within the human genome...
  33. Sharp R, Beg S, Naser S. Role of PTPN2/22 polymorphisms in pathophysiology of Crohn's disease. World J Gastroenterol. 2018;24:657-670 pubmed publisher
    To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease (CD)...
  34. Aradi B, Kato M, Filková M, Karouzakis E, Klein K, Scharl M, et al. Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 production in rheumatoid arthritis synovial fibroblasts. Arthritis Rheumatol. 2015;67:2624-33 pubmed publisher
    To investigate the role of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in the pathogenesis of rheumatoid arthritis (RA)...
  35. Kim W, Koo J, Cho H, Lee J, Kim J, Lee H, et al. Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis. J Allergy Clin Immunol. 2018;141:137-151 pubmed publisher
    ..We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis. ..
  36. Penafuerte C, Pérez Quintero L, Vinette V, Hatzihristidis T, Tremblay M. Mining the Complex Family of Protein Tyrosine Phosphatases for Checkpoint Regulators in Immunity. Curr Top Microbiol Immunol. 2017;410:191-214 pubmed publisher
    ..Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-..
  37. Pike K, Hatzihristidis T, Bussières Marmen S, Robert F, Desai N, Miranda Saavedra D, et al. TC-PTP regulates the IL-7 transcriptional response during murine early T cell development. Sci Rep. 2017;7:13275 pubmed publisher
    ..Here, we have identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell ..
  38. Abdjul D, Yamazaki H, Kanno S, Wewengkang D, Rotinsulu H, Sumilat D, et al. Furanoterpenes, new types of protein tyrosine phosphatase 1B inhibitors, from two Indonesian marine sponges, Ircinia and Spongia spp. Bioorg Med Chem Lett. 2017;27:1159-1161 pubmed publisher
    ..5, 7.1, and 9.9?M, respectively. The inhibitory activity of compound 1 against T-cell PTP (TCPTP) was approximately 2-fold that against PTP1B, whereas the vaccinia H-1-related phosphatase (VHR) inhibitory ..
  39. Fu H, Leung S, Yam V. A rational molecular design of triazine-containing alkynylplatinum(ii) terpyridine complexes and the formation of helical ribbons via PtPt, π-π stacking and hydrophobic-hydrophobic interactions. Chem Commun (Camb). 2017;53:11349-11352 pubmed publisher
    ..Fine control of the morphological transition from plates to helical structures has been demonstrated through an interplay of the bent molecular structure and PtPt, π-π stacking and hydrophobic-hydrophobic interactions.
  40. Yu W, Hegarty J, Berg A, Kelly A, Wang Y, Poritz L, et al. PTPN2 is associated with Crohn's disease and its expression is regulated by NKX2-3. Dis Markers. 2012;32:83-91 pubmed publisher
    b>PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry...
  41. Bukczynska P, Klingler Hoffmann M, Mitchelhill K, Lam M, Ciccomancini M, Tonks N, et al. The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis. Biochem J. 2004;380:939-49 pubmed
    Two alternatively spliced forms of the human protein tyrosine phosphatase TCPTP (T-cell protein tyrosine phosphatase) exist: a 48 kDa form that is targeted to the endoplasmic reticulum (TC48) and a shorter 45 kDa form that is targeted to ..
  42. Meng T, Buckley D, Galic S, Tiganis T, Tonks N. Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B. J Biol Chem. 2004;279:37716-25 pubmed
  43. Huang H, Liu N, Liao Y, Liu N, Cai J, Xia X, et al. Platinum-containing compound platinum pyrithione suppresses ovarian tumor proliferation through proteasome inhibition. J Exp Clin Cancer Res. 2017;36:79 pubmed publisher
    ..Nude mouse experiment was performed to test the in vivo effect of platinum pyrithione (PtPT)...
  44. Gusman C, Viana A, Miranda M, Pedrosa M, Villela W. [Inclusion of traditional birth attendants in the public health care system in Brazil: reflecting on challenges]. Rev Panam Salud Publica. 2015;37:365-70 pubmed
    ..of traditional birth attendants for the Health Ministry's Working with Traditional Birth Attendants Program (PTPT)...
  45. Klingler Hoffmann M, Fodero Tavoletti M, Mishima K, Narita Y, Cavenee W, Furnari F, et al. The protein tyrosine phosphatase TCPTP suppresses the tumorigenicity of glioblastoma cells expressing a mutant epidermal growth factor receptor. J Biol Chem. 2001;276:46313-8 pubmed
    ..Here, we report that the 45-kDa variant of the protein tyrosine phosphatase TCPTP (TC45) can recognize Delta EGFR as a cellular substrate...
  46. Zhao C, Chen X, Zang D, Lan X, Liao S, Yang C, et al. Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy. Biochem Pharmacol. 2016;116:22-38 pubmed publisher
    ..Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits ..
  47. Li X, Xu Q, Luo J, Wang L, Jiang B, Zhang R, et al. Design, synthesis and biological evaluation of uncharged catechol derivatives as selective inhibitors of PTP1B. Eur J Med Chem. 2017;136:348-359 pubmed publisher
    ..487 ?M against PTP1B and strong selectivity (27-fold) over TCPTP. Kinetic studies were also performed that 22 act as a competitive PTP1B inhibitor...
  48. Liu P, Du Y, Song L, Shen J, Li Q. Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity. Eur J Med Chem. 2016;118:27-33 pubmed publisher
    ..exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP)...
  49. Wu R, He Q, Chen H, Xu M, Zhao N, Xiao Y, et al. MicroRNA-448 promotes multiple sclerosis development through induction of Th17 response through targeting protein tyrosine phosphatase non-receptor type 2 (PTPN2). Biochem Biophys Res Commun. 2017;486:759-766 pubmed publisher
    ..Additionally, we identified that miR-448 directly targeted protein tyrosine phosphatase non-receptor type 2 (PTPN2), which has been known as an anti-inflammatory player with capacity to suppress Th17 differentiation...
  50. Gubiani J, Wijeratne E, Shi T, Araujo A, Arnold A, Chapman E, et al. An epigenetic modifier induces production of (10'S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla. Bioorg Med Chem. 2017;25:1860-1866 pubmed publisher
    ..of protein tyrosine phosphatases (PTPs) 1B (PTP1B), Src homology 2-containing PTP 1 (SHP1) and T-cell PTP (TCPTP) with IC50 values of 13.7±3.4, 8.8±0.6, and 16.6±3.8μM, respectively...
  51. Alberdi Saugstrup M, Enevold C, Zak M, Nielsen S, Nordal E, Berntson L, et al. Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome. Scand J Rheumatol. 2017;46:369-376 pubmed publisher
    ..Evidence of associations between genotypes and endpoints were found for STAT4, ADAD1-IL2-IL21, PTPN2, and VTCN1 (p = 0.003-0.05)...
  52. Ellis J, Scurrah K, Li Y, Ponsonby A, Chavez R, Pezic A, et al. Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis. J Steroid Biochem Mol Biol. 2015;145:113-20 pubmed publisher
    ..b>PTPN2, a vitamin D responsive gene, is a confirmed susceptibility gene in JIA, and PTPN2 has been suggested to interact ..
  53. Shimizu T, Miyakawa Y, Iwata S, Kuribara A, Tiganis T, Morimoto C, et al. A novel mechanism for imatinib mesylate (STI571) resistance in CML cell line KT-1: role of TC-PTP in modulating signals downstream from the BCR-ABL fusion protein. Exp Hematol. 2004;32:1057-63 pubmed
    ..b>T cell protein tyrosine phosphatase (TC-PTP) was markedly downregulated in all KTR cells compared to parental KT-1 cells...
  54. Muppirala M, Gupta V, Swarup G. Emerging role of tyrosine phosphatase, TCPTP, in the organelles of the early secretory pathway. Biochim Biophys Acta. 2013;1833:1125-32 pubmed publisher
    T-cell protein tyrosine phosphatase, TCPTP, is a ubiquitously expressed non-receptor type tyrosine phosphatase. There are two splice variants of TCPTP, TC48 and TC45, which differ in their sub-cellular localizations and functions...
  55. Scharl M, Rudenko I, McCole D. Loss of protein tyrosine phosphatase N2 potentiates epidermal growth factor suppression of intestinal epithelial chloride secretion. Am J Physiol Gastrointest Liver Physiol. 2010;299:G935-45 pubmed publisher
    The Crohn's disease candidate gene, protein tyrosine phosphatase nonreceptor type 2 (PTPN2), has been shown to regulate epidermal growth factor (EGF)-induced phosphatidylinositol 3-kinase (PI3K) activation in fibroblasts...
  56. Mitra A, Sasikumar K, Parthasaradhi B, Radha V. The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. Biochim Biophys Acta. 2013;1832:275-84 pubmed publisher
    ..This study investigated the ability of the intracellular T cell protein tyrosine phosphatase (TCPTP/PTPN2) to dephosphorylate and regulate the functions of BCR-Abl and c-Abl...
  57. Dodd G, Andrews Z, Simonds S, Michael N, DeVeer M, Brüning J, et al. A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding. Cell Metab. 2017;26:375-393.e7 pubmed publisher
    ..for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons,..
  58. Yoo T, Ham S, Lee W, Hwang S, Park J, Hwang J, et al. Ligand-Dependent Interaction of PPAR? With T-Cell Protein Tyrosine Phosphatase 45 Enhances Insulin Signaling. Diabetes. 2018;67:360-371 pubmed publisher
    ..This novel interaction of PPAR? constitutes the most upstream component identified of the mechanism downregulating insulin signaling. ..
  59. Cobb J, Plant D, Flynn E, Tadjeddine M, Dieudé P, Cornélis F, et al. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans. PLoS ONE. 2013;8:e66456 pubmed publisher
    ..Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-..
  60. Liao H, Pei D. Cell-permeable bicyclic peptidyl inhibitors against T-cell protein tyrosine phosphatase from a combinatorial library. Org Biomol Chem. 2017;15:9595-9598 pubmed publisher
    ..In this study, we developed cell-permeable bicyclic peptidyl inhibitors against T-cell PTP (TCPTP), which feature a cell-penetrating motif in one ring and a target-binding sequence in the second ring.
  61. Chen X, Yang Q, Xiao L, Tang D, Dou Q, Liu J. Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents. Cancer Metastasis Rev. 2017;36:655-668 pubmed publisher
    ..copper pyrithione (CuPT) and zinc pyrithione (ZnPT), and also our two synthesized complexes platinum pyrithione (PtPT) and nickel pyrithione (NiPT), can target the proteasomal DUBs UCHL5 and USP14...
  62. St Germain J, Taylor P, Zhang W, Li Z, Ketela T, Moffat J, et al. Differential regulation of FGFR3 by PTPN1 and PTPN2. Proteomics. 2015;15:419-33 pubmed publisher
    ..Knockdown of PTPN1 or the related enzyme PTPN2 by RNAi resulted in ligand-independent activation of FGFR3...
  63. Wu Z, Chen H, Sun F, Xu J, Zheng W, Li P, et al. PTPN2 rs1893217 single-nucleotide polymorphism is associated with risk of Behçet's disease in a Chinese Han population. Clin Exp Rheumatol. 2014;32:S20-6 pubmed
    ..This study investigated single-nucleotide polymorphisms (SNP) of tyrosine-protein phosphatase non-receptor type 2 (PTPN2) and inducible T-cell co-stimulator-ligand gene (ICOSLG) in Chinese Han BD patients and healthy controls because ..
  64. Shields B, Wiede F, Gurzov E, Wee K, Hauser C, Zhu H, et al. TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers. Mol Cell Biol. 2013;33:557-70 pubmed publisher
    ..EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2)...
  65. Frederiksen B, Liu E, Romanos J, Steck A, Yin X, Kroehl M, et al. Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). J Steroid Biochem Mol Biol. 2013;133:51-7 pubmed publisher
    ..between variants in the vitamin D receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet autoimmunity (IA) and progression to type ..
  66. Ferrero G, Velazquez F, Caputto B. The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos tyrosine phosphorylation and c-Fos phospholipid synthesis activation capacity. Oncogene. 2012;31:3381-91 pubmed publisher
    ..Activated TC45 in its turn promotes dephosphorylation of pre-formed c-Fos, enabling cells to rapidly activate phospholipid synthesis to respond to its growth demands. ..
  67. Wiede F, Shields B, Chew S, Kyparissoudis K, van Vliet C, Galic S, et al. T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. J Clin Invest. 2011;121:4758-74 pubmed publisher
    ..Single nucleotide polymorphisms in PTPN2, which encodes T cell protein tyrosine phosphatase (TCPTP), have been linked with the development of several autoimmune diseases, including type 1 ..
  68. Kleppe M, Tousseyn T, Geissinger E, Kalender Atak Z, Aerts S, Rosenwald A, et al. Mutation analysis of the tyrosine phosphatase PTPN2 in Hodgkin's lymphoma and T-cell non-Hodgkin's lymphoma. Haematologica. 2011;96:1723-7 pubmed publisher
    We recently reported deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia...
  69. Sakamoto S, Qin J, Navarro A, Gamero A, Potla R, Yi T, et al. Cells previously desensitized to type 1 interferons display different mechanisms of activation of stat-dependent gene expression from naïve cells. J Biol Chem. 2004;279:3245-53 pubmed
    ..These results implicate Tc-PTP in a novel role in the regulation of type 1 interferon-stimulated gene expression. ..
  70. Omerovic J, Clague M, Prior I. Phosphatome profiling reveals PTPN2, PTPRJ and PTEN as potent negative regulators of PKB/Akt activation in Ras-mutated cancer cells. Biochem J. 2010;426:65-72 pubmed publisher
    ..Importantly, we identified other phosphatases with similar potencies including PTPN2 (T-cell protein tyrosine phosphatase; also known as TC-PTP) and PTPRJ (protein tyrosine phosphatase receptor type ..
  71. Kramer O, Knauer S, Greiner G, Jandt E, Reichardt S, Gührs K, et al. A phosphorylation-acetylation switch regulates STAT1 signaling. Genes Dev. 2009;23:223-35 pubmed publisher
    ..These findings reveal a new layer of physiologically relevant STAT1 regulation and suggest that a previously unidentified balance between phosphorylation and acetylation affects cytokine signaling. ..
  72. Wu C, Kraft P, Zhai K, Chang J, Wang Z, Li Y, et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet. 2012;44:1090-7 pubmed publisher
    ..Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption. ..
  73. Cooper J, Smyth D, Smiles A, Plagnol V, Walker N, Allen J, et al. Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008;40:1399-401 pubmed publisher
    ..7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)). ..