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Gene Review

Ptpn6  -  protein tyrosine phosphatase, non-receptor...

Mus musculus

Synonyms: 70Z-SHP, Hcp, Hcph, Hematopoietic cell protein-tyrosine phosphatase, PTP-1C, ...
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Disease relevance of Ptpn6


High impact information on Ptpn6


Chemical compound and disease context of Ptpn6


Biological context of Ptpn6


Anatomical context of Ptpn6

  • The motheaten mutation rescues B cell signaling and development in CD45-deficient mice [11].
  • Surprisingly, however, the presence or absence of SHP1 had no effect on the proliferative response of bone marrow-derived cultured mast cells to KL or IL3 ex vivo [14].
  • These mice are essentially SHPTP1 null and display multiple hematopoietic abnormalities, most prominently hyperproliferation and inappropriate activation of granulocytes and macrophages [12].
  • Furthermore, transduction of primary hematopoietic progenitor cells from viable motheaten mice with these mutant Gab2 molecules also significantly ameliorated their enhanced migration capacity associated with the SHP1 gene mutation [15].
  • SHP-1 is an SH2-containing cytoplasmic tyrosine phosphatase that is widely distributed in cells of the hematopoietic system [13].

Associations of Ptpn6 with chemical compounds


Physical interactions of Ptpn6


Enzymatic interactions of Ptpn6

  • P130 and SHPTP1 are further tyrosyl phosphorylated upon CSF-1 stimulation [12].
  • The Ets2 transcription factor is constitutively phosphorylated on residue Thr(72) in macrophages derived from mice homozygous for the motheaten viable (me-v) allele of the hemopoietic cell phosphatase (Hcph) gene [22].
  • The biochemical basis of this complex trait involves a pathway requiring Lyn to phosphorylate CD22 and recruit SHP-1 to the CD22/BCR complex [23].

Regulatory relationships of Ptpn6

  • Using primary bone marrow-derived macrophages from me/me mice and normal littermates, we examined the role of SHPTP1 in regulating signaling by the major macrophage mitogen colony-stimulating factor 1 (CSF-1) (also known as macrophage colony-stimulating factor) [12].
  • Fas-induced DNA degradation detected by the terminal deoxynucleotide transferase reaction was also observed in the killing of motheaten thymocytes by a Fas-based CTL as well as by anti-Fas mAb [24].
  • Finally, introduction of purified Leishmania EF-1alpha, but not the corresponding host protein into macrophages activated SHP-1 and blocked the induction of inducible nitric-oxide synthase expression in response to interferon-gamma [25].
  • We prepared Et-3,4-dephostatin as a stable analogue and found it to inhibit PTP-1B and SHPTP-1 protein-tyrosine phosphatases selectively but not to inhibit CD45 and leukocyte common antigen-related phosphatase ones effectively [26].
  • The activity of src-homology 2 domain-containing PTP (SHP-1) was significantly upregulated 1 min after AT2 stimulation [27].

Other interactions of Ptpn6

  • These proteins are hyperphosphorylated on tyrosyl residues in me/me macrophages, suggesting that Grb2 may recruit substrates for SHPTP1 [12].
  • Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1 [12].
  • Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model [22].
  • Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in the regulation of interleukin-3-induced survival, proliferation and signalling [28].
  • Interestingly, several markedly hyperphosphorylated proteins were detected in the motheaten macrophages, including a novel 126-kDa phosphotyrosine protein that associated with the phosphatase via its SH2 domains, suggesting that these proteins depend on HCP for dephosphorylation and may mediate the heightened growth responses to GM-CSF [3].

Analytical, diagnostic and therapeutic context of Ptpn6


  1. Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor. Su, X., Zhou, T., Yang, P., Edwards, C.K., Mountz, J.D. Arthritis Rheum. (1998) [Pubmed]
  2. Receptor activator of NF-kappa B ligand stimulates recruitment of SHP-1 to the complex containing TNFR-associated factor 6 that regulates osteoclastogenesis. Zhang, Z., Jimi, E., Bothwell, A.L. J. Immunol. (2003) [Pubmed]
  3. Macrophages from motheaten and viable motheaten mutant mice show increased proliferative responses to GM-CSF: detection of potential HCP substrates in GM-CSF signal transduction. Jiao, H., Yang, W., Berrada, K., Tabrizi, M., Shultz, L., Yi, T. Exp. Hematol. (1997) [Pubmed]
  4. Role of tumor necrosis factor-alpha in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Thrall, R.S., Vogel, S.N., Evans, R., Shultz, L.D. Am. J. Pathol. (1997) [Pubmed]
  5. Signalling by the W/Kit receptor tyrosine kinase is negatively regulated in vivo by the protein tyrosine phosphatase Shp1. Paulson, R.F., Vesely, S., Siminovitch, K.A., Bernstein, A. Nat. Genet. (1996) [Pubmed]
  6. Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Klingmüller, U., Lorenz, U., Cantley, L.C., Neel, B.G., Lodish, H.F. Cell (1995) [Pubmed]
  7. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Shultz, L.D., Schweitzer, P.A., Rajan, T.V., Yi, T., Ihle, J.N., Matthews, R.J., Thomas, M.L., Beier, D.R. Cell (1993) [Pubmed]
  8. Sodium stibogluconate interacts with IL-2 in anti-Renca tumor action via a T cell-dependent mechanism in connection with induction of tumor-infiltrating macrophages. Fan, K., Zhou, M., Pathak, M.K., Lindner, D.J., Altuntas, C.Z., Tuohy, V.K., Borden, E.C., Yi, T. J. Immunol. (2005) [Pubmed]
  9. Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis. Forget, G., Siminovitch, K.A., Brochu, S., Rivest, S., Radzioch, D., Olivier, M. Eur. J. Immunol. (2001) [Pubmed]
  10. The tyrosine phosphatase SHP-1 is a negative regulator of osteoclastogenesis and osteoclast resorbing activity: increased resorption and osteopenia in me(v)/me(v) mutant mice. Aoki, K., Didomenico, E., Sims, N.A., Mukhopadhyay, K., Neff, L., Houghton, A., Amling, M., Levy, J.B., Horne, W.C., Baron, R. Bone (1999) [Pubmed]
  11. The motheaten mutation rescues B cell signaling and development in CD45-deficient mice. Pani, G., Siminovitch, K.A., Paige, C.J. J. Exp. Med. (1997) [Pubmed]
  12. Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1. Chen, H.E., Chang, S., Trub, T., Neel, B.G. Mol. Cell. Biol. (1996) [Pubmed]
  13. Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1. Jiao, H., Berrada, K., Yang, W., Tabrizi, M., Platanias, L.C., Yi, T. Mol. Cell. Biol. (1996) [Pubmed]
  14. Genetic analysis reveals cell type-specific regulation of receptor tyrosine kinase c-Kit by the protein tyrosine phosphatase SHP1. Lorenz, U., Bergemann, A.D., Steinberg, H.N., Flanagan, J.G., Li, X., Galli, S.J., Neel, B.G. J. Exp. Med. (1996) [Pubmed]
  15. Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migration. Yu, W.M., Hawley, T.S., Hawley, R.G., Qu, C.K. Blood (2002) [Pubmed]
  16. Deficiency of SHP-1 protein-tyrosine phosphatase activity results in heightened osteoclast function and decreased bone density. Umeda, S., Beamer, W.G., Takagi, K., Naito, M., Hayashi, S., Yonemitsu, H., Yi, T., Shultz, L.D. Am. J. Pathol. (1999) [Pubmed]
  17. The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. Roach, T.I., Slater, S.E., White, L.S., Zhang, X., Majerus, P.W., Brown, E.J., Thomas, M.L. Curr. Biol. (1998) [Pubmed]
  18. The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate. Berg, K.L., Carlberg, K., Rohrschneider, L.R., Siminovitch, K.A., Stanley, E.R. Oncogene (1998) [Pubmed]
  19. SHP-1 inhibits LPS-mediated TNF and iNOS production in murine macrophages. Hardin, A.O., Meals, E.A., Yi, T., Knapp, K.M., English, B.K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  20. T cell developmental defects in 'viable motheaten' mice deficient in SHP-1 protein-tyrosine phosphatase. Developmental defects are corrected in vitro in the presence of normal hematopoietic-origin stromal cells and in vivo by exogenous IL-7. Christianson, S.W., Greiner, D.L., Deluca, D., Leif, J., Phillips, N.E., Hayes, S.M., Hayashi, S., Joliat, M.J., Lyons, B.L., Shultz, L.D. J. Autoimmun. (2002) [Pubmed]
  21. Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase. Liedtke, M., Pandey, P., Kumar, S., Kharbanda, S., Kufe, D. Oncogene (1998) [Pubmed]
  22. Activated Ets2 is required for persistent inflammatory responses in the motheaten viable model. Wei, G., Guo, J., Doseff, A.I., Kusewitt, D.F., Man, A.K., Oshima, R.G., Ostrowski, M.C. J. Immunol. (2004) [Pubmed]
  23. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Cornall, R.J., Cyster, J.G., Hibbs, M.L., Dunn, A.R., Otipoby, K.L., Clark, E.A., Goodnow, C.C. Immunity (1998) [Pubmed]
  24. Lack of requirement for SHP-1 in both Fas-mediated and perforin-mediated cell death induced by CTL. Takayama, H., Lee, M.H., Shirota-Someya, Y. J. Immunol. (1996) [Pubmed]
  25. Leishmania EF-1alpha activates the Src homology 2 domain containing tyrosine phosphatase SHP-1 leading to macrophage deactivation. Nandan, D., Yi, T., Lopez, M., Lai, C., Reiner, N.E. J. Biol. Chem. (2002) [Pubmed]
  26. Potentiation of insulin-related signal transduction by a novel protein-tyrosine phosphatase inhibitor, Et-3,4-dephostatin, on cultured 3T3-L1 adipocytes. Suzuki, T., Hiroki, A., Watanabe, T., Yamashita, T., Takei, I., Umezawa, K. J. Biol. Chem. (2001) [Pubmed]
  27. Effect of angiotensin II type 2 receptor on tyrosine kinase Pyk2 and c-Jun NH2-terminal kinase via SHP-1 tyrosine phosphatase activity: evidence from vascular-targeted transgenic mice of AT2 receptor. Matsubara, H., Shibasaki, Y., Okigaki, M., Mori, Y., Masaki, H., Kosaki, A., Tsutsumi, Y., Uchiyama, Y., Fujiyama, S., Nose, A., Iba, O., Tateishi, E., Hasegawa, T., Horiuchi, M., Nahmias, C., Iwasaka, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  28. Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in the regulation of interleukin-3-induced survival, proliferation and signalling. Paling, N.R., Welham, M.J. Biochem. J. (2002) [Pubmed]
  29. Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1. Brockdorff, J., Williams, S., Couture, C., Mustelin, T. Eur. J. Immunol. (1999) [Pubmed]
  30. Aberrant expression of the NF-kappaB and IkappaB proteins in B cells from viable motheaten mice. Khaled, A.R., Butfiloski, E.J., Villas, B., Sobel, E.S., Schiffenbauer, J. Autoimmunity (1999) [Pubmed]
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