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Gene Review

PTPN2  -  protein tyrosine phosphatase, non-receptor...

Homo sapiens

Synonyms: PTN2, PTPT, T-cell protein-tyrosine phosphatase, TC-PTP, TCELLPTP, ...
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Disease relevance of PTPN2


High impact information on PTPN2

  • Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP [7].
  • The cytoplasmic 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 [8].
  • We found distinct expression profiles of tyrosine phosphatases in DLBCL subtypes and identified putative STAT6 tyrosine phosphatases-protein tyrosine phosphatase nonreceptor type 1 (PTPN1) and PTPN2, whose expression is significantly higher in ABC-like DLBCL [9].
  • Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling [10].
  • We have now purified a Stat1 PTP activity from HeLa cell nuclear extract and identified it as TC45, the nuclear isoform of the T-cell PTP (TC-PTP) [11].

Chemical compound and disease context of PTPN2


Biological context of PTPN2


Anatomical context of PTPN2

  • Reconstitution of TC-PTP-null MEFs with TC45, but not the endoplasmic reticulum (ER)-associated isoform TC48, rescues the defect in Stat1 dephosphorylation [11].
  • Furthermore, the dephosphorylation of IFN-induced tyrosine-phosphorylated Stat1 is defective in TC-PTP-null mouse embryonic fibroblasts (MEFs) and primary thymocytes [11].
  • The TCPTP D182A substrate-trapping mutants were transiently overexpressed in COS cells, and their ability to form complexes with tyrosine-phosphorylated (pTyr) proteins was assessed [13].
  • 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 [16].
  • We show that the proliferative response of lymphocytes was greatly increased when cultured as a purified population, indicating that an inhibitory population is present in TC-PTP(-/-) spleen [17].

Associations of PTPN2 with chemical compounds

  • To identify TCPTP substrates, we have generated substrate-trapping mutants, in which the invariant catalytic acid of TCPTP (D182) is mutated to alanine [13].
  • Therefore, we examined whether the suppression of TC-PTP expression might contribute to imatinib mesylate-resistance in KTR cells [16].
  • Unlike wild-type TCPTP, the R49K derivative preferred tyrosine to aspartic or glutamic acid [18].
  • Cys 121 is highly conserved among phosphatases, and ABDF also inhibits TC-PTP and LAR [19].
  • With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site [20].

Physical interactions of PTPN2


Enzymatic interactions of PTPN2


Regulatory relationships of PTPN2

  • Here, we demonstrate that IL-6-induced tyrosine-phosphorylation and activation of STAT3 were suppressed by overexpression of the nuclear isoform of TC-PTP in 293T cells [1].

Other interactions of PTPN2


Analytical, diagnostic and therapeutic context of PTPN2

  • By affinity chromatography, using GST-TCPTP fusion proteins, we have isolated three cytoplasmic proteins of 120, 116, and 97 kDa that interact with TCPTP [14].
  • We show that a Gr-1(+)-enriched cell population isolated from TC-PTP(-/-) mice suppresses the CD3-induced proliferation of T cells in coculture in vitro [17].
  • Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs [24].
  • Sequences specific to and homologous to human T-cell PTPase (TC-PTP) were found in the genomic clones of PTP-S, which are expressed in rat cells, as determined by using a specific probe and Northern blot analysis [25].
  • Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs, activated PDGF beta-receptors colocalized with Rab4a, a marker for rapid recycling [26].



  1. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Yamamoto, T., Sekine, Y., Kashima, K., Kubota, A., Sato, N., Aoki, N., Matsuda, T. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  2. Involvement of the small protein tyrosine phosphatases TC-PTP and PTP1B in signal transduction and diseases: from diabetes, obesity to cell cycle, and cancer. Dubé, N., Tremblay, M.L. Biochim. Biophys. Acta (2005) [Pubmed]
  3. Self-complementary adeno-associated virus 2 (AAV)-T cell protein tyrosine phosphatase vectors as helper viruses to improve transduction efficiency of conventional single-stranded AAV vectors in vitro and in vivo. Zhong, L., Chen, L., Li, Y., Qing, K., Weigel-Kelley, K.A., Chan, R.J., Yoder, M.C., Srivastava, A. Mol. Ther. (2004) [Pubmed]
  4. Adeno-associated virus type 2-mediated gene transfer: role of cellular T-cell protein tyrosine phosphatase in transgene expression in established cell lines in vitro and transgenic mice in vivo. Qing, K., Li, W., Zhong, L., Tan, M., Hansen, J., Weigel-Kelley, K.A., Chen, L., Yoder, M.C., Srivastava, A. J. Virol. (2003) [Pubmed]
  5. Purification and characterization of a human recombinant T-cell protein-tyrosine-phosphatase from a baculovirus expression system. Zander, N.F., Lorenzen, J.A., Cool, D.E., Tonks, N.K., Daum, G., Krebs, E.G., Fischer, E.H. Biochemistry (1991) [Pubmed]
  6. Increased susceptibility to dextran sulfate sodium induced colitis in the T cell protein tyrosine phosphatase heterozygous mouse. Hassan, S.W., Doody, K.M., Hardy, S., Uetani, N., Cournoyer, D., Tremblay, M.L. PLoS. One. (2010) [Pubmed]
  7. Cytoplasmic protein tyrosine phosphatases, regulation and function: the roles of PTP1B and TC-PTP. Bourdeau, A., Dubé, N., Tremblay, M.L. Curr. Opin. Cell Biol. (2005) [Pubmed]
  8. Negative regulation of EGFR signalling through integrin-alpha1beta1-mediated activation of protein tyrosine phosphatase TCPTP. Mattila, E., Pellinen, T., Nevo, J., Vuoriluoto, K., Arjonen, A., Ivaska, J. Nat. Cell Biol. (2005) [Pubmed]
  9. Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas. Lu, X., Nechushtan, H., Ding, F., Rosado, M.F., Singal, R., Alizadeh, A.A., Lossos, I.S. Blood (2005) [Pubmed]
  10. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Galic, S., Hauser, C., Kahn, B.B., Haj, F.G., Neel, B.G., Tonks, N.K., Tiganis, T. Mol. Cell. Biol. (2005) [Pubmed]
  11. Identification of a nuclear Stat1 protein tyrosine phosphatase. ten Hoeve, J., de Jesus Ibarra-Sanchez, M., Fu, Y., Zhu, W., Tremblay, M., David, M., Shuai, K. Mol. Cell. Biol. (2002) [Pubmed]
  12. 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. Johnson, C.V., Cool, D.E., Glaccum, M.B., Green, N., Fischer, E.H., Bruskin, A., Hill, D.E., Lawrence, J.B. Genomics (1993) [Pubmed]
  13. Epidermal growth factor receptor and the adaptor protein p52Shc are specific substrates of T-cell protein tyrosine phosphatase. Tiganis, T., Bennett, A.M., Ravichandran, K.S., Tonks, N.K. Mol. Cell. Biol. (1998) [Pubmed]
  14. Association of the T-cell protein tyrosine phosphatase with nuclear import factor p97. Tiganis, T., Flint, A.J., Adam, S.A., Tonks, N.K. J. Biol. Chem. (1997) [Pubmed]
  15. Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase. Zhu, W., Mustelin, T., David, M. J. Biol. Chem. (2002) [Pubmed]
  16. 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. Shimizu, T., Miyakawa, Y., Iwata, S., Kuribara, A., Tiganis, T., Morimoto, C., Ikeda, Y., Kizaki, M. Exp. Hematol. (2004) [Pubmed]
  17. Gr-1+ myeloid cells lacking T cell protein tyrosine phosphatase inhibit lymphocyte proliferation by an IFN-gamma- and nitric oxide-dependent mechanism. Dupuis, M., De Jesús Ibarra-Sánchez, M., Tremblay, M.L., Duplay, P. J. Immunol. (2003) [Pubmed]
  18. The YRD motif is a major determinant of substrate and inhibitor specificity in T-cell protein-tyrosine phosphatase. Asante-Appiah, E., Ball, K., Bateman, K., Skorey, K., Friesen, R., Desponts, C., Payette, P., Bayly, C., Zamboni, R., Scapin, G., Ramachandran, C., Kennedy, B.P. J. Biol. Chem. (2001) [Pubmed]
  19. Allosteric inhibition of PTP1B activity by selective modification of a non-active site cysteine residue. Hansen, S.K., Cancilla, M.T., Shiau, T.P., Kung, J., Chen, T., Erlanson, D.A. Biochemistry (2005) [Pubmed]
  20. Potent, selective inhibitors of protein tyrosine phosphatase 1B. Xin, Z., Oost, T.K., Abad-Zapatero, C., Hajduk, P.J., Pei, Z., Szczepankiewicz, B.G., Hutchins, C.W., Ballaron, S.J., Stashko, M.A., Lubben, T., Trevillyan, J.M., Jirousek, M.R., Liu, G. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
  21. Purification and characterization of T cell protein tyrosine phosphatase reveals significant functional homology to protein tyrosine phosphatase-1B. Romsicki, Y., Kennedy, B.P., Asante-Appiah, E. Arch. Biochem. Biophys. (2003) [Pubmed]
  22. The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis. Bukczynska, P., Klingler-Hoffmann, M., Mitchelhill, K.I., Lam, M.H., Ciccomancini, M., Tonks, N.K., Sarcevic, B., Kemp, B.E., Tiganis, T. Biochem. J. (2004) [Pubmed]
  23. The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling. Mattila, E., Auvinen, K., Salmi, M., Ivaska, J. J. Cell. Sci. (2008) [Pubmed]
  24. Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases. Iversen, L.F., Andersen, H.S., Møller, K.B., Olsen, O.H., Peters, G.H., Branner, S., Mortensen, S.B., Hansen, T.K., Lau, J., Ge, Y., Holsworth, D.D., Newman, M.J., Hundahl Møller, N.P. Biochemistry (2001) [Pubmed]
  25. Alternative splicing generates four different forms of a non-transmembrane protein tyrosine phosphatase mRNA. Reddy, R.S., Swarup, G. DNA Cell Biol. (1995) [Pubmed]
  26. Loss of T-Cell Protein Tyrosine Phosphatase Induces Recycling of the Platelet-derived Growth Factor (PDGF) beta-Receptor but Not the PDGF {alpha}-Receptor. Karlsson, S., Kowanetz, K., Sandin, A., Persson, C., Ostman, A., Heldin, C.H., Hellberg, C. Mol. Biol. Cell (2006) [Pubmed]
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