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Gene Review

Ptprc  -  protein tyrosine phosphatase, receptor...

Mus musculus

Synonyms: B220, CD45, CD45R, Cd45, L-CA, ...
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Disease relevance of Ptprc

  • The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220 [1].
  • The CD45 E613R mutation causes polyclonal lymphocyte activation leading to lymphoproliferation and severe autoimmune nephritis with autoantibody production, resulting in death [2].
  • We now show that mice expressing active lck(F505) at non-oncogenic levels develop aggressive thymic lymphomas on a CD45(-/-) background [3].
  • Expression of the CD45 Ag in hemopoietic cells is essential for normal development and function of lymphocytes, and both mice and humans lacking expression exhibit SCID [4].
  • Human genetic variants of CD45, the exon 4 C77G and exon 6 A138G alleles, which alter the pattern of CD45 isoform expression, are associated with autoimmune and infectious diseases [4].
  • To date, this is the first report demonstrating that reduced levels of host phosphatase CD45 modulate anthrax pathogenesis [5].

Psychiatry related information on Ptprc

  • In addition, we show that T cells from CD45RO and CD45ABC mice accumulate in lymph nodes but not in the spleen, liver, or skin, indicating that the CD45 phosphatase may control the homing behavior and trafficking of T cells [6].
  • Reactive microglia have been suggested to play a role in the Alzheimer's disease (AD) process, and previous studies have shown that expression of CD45, a membrane-bound protein-tyrosine phosphatase (PTP), is elevated in microglia in AD brain compared with controls [7].
  • Administration of B-220 1 h before TPA promotion resulted in a prolonged latency period of tumor appearance and a significantly reduced (up to 15% of positive controls) papilloma yield at 20 weeks [8].
  • In reactive disorders, a population of activated neutrophils with high CD45 and CD18 expression was detected [9].

High impact information on Ptprc

  • CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process [10].
  • Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity [10].
  • It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors [10].
  • The dramatic phenotype of CD45 E613R mice demonstrates the in vivo importance of negative regulation of CD45 by dimerization, supporting the model for regulation of CD45, and RPTPs in general [2].
  • A model has been proposed for the regulation of CD45, and by homology other RPTPs, in which dimerization inhibits phosphatase activity through symmetrical interactions between an inhibitory structural wedge and the catalytic site [2].

Chemical compound and disease context of Ptprc

  • The present study addressed T-cell-independent B cell responses in CD45-deficient mice using the glycoprotein (G) of vesicular stomatitis virus (VSV) as a model antigen [11].
  • Recently a gain of function mutation in CD45 that may enhance activity of Src family tyrosine kinases has also been found to cause autoimmune disease, suggesting that the level of Src family tyrosine kinase activity is an important determinant of immune tolerance [12].
  • Fractionation of membrane vesicles prepared from BW5147 lymphoma cells by sedimentation through sucrose density gradients show that antigens T25 and T200 are in fractions enriched with plasma membrane [13].
  • Here we present evidence that the transmembrane phosphotyrosine phosphatase CD45 critically regulates TCR-induced signals in thymic differentiation and present data to show defective depletion of CD45-null transgenic TCR-Vbeta8 DP thymocytes in FTOC by the Staphylococcus aureus Enterotoxin B (SEB) superantigen [14].

Biological context of Ptprc


Anatomical context of Ptprc

  • Furthermore, HSCs in Runx1(+/-) embryos are heterogeneous and include CD45(+) cells, endothelial cells, and mesenchymal cells [19].
  • To determine whether these PTPs act independently or coordinately in modulating the physiologic outcome of BCR engagement, we assessed B cell development and signaling in CD45-deficient mev (CD45-/SHP-1-) mice [15].
  • In this study we investigate the role of the cell surface phosphatase CD45 in NK cell development and intracellular signaling from activating receptors [16].
  • RNA transfer blotting using a cDNA probe encoding this sequence established that the predominant T200 mRNA species from B cells and cytotoxic T-cell clones but not T-helper cell clones or thymocytes contain all or part of the insert [20].
  • Here we describe in I/RC hearts a population of small spindle-shaped fibroblasts that were highly proliferative and expressed collagen I and alpha-smooth muscle actin (myofibroblast markers), CD34 (a precursor marker), and CD45 (a hematopoietic marker) [21].

Associations of Ptprc with chemical compounds

  • In addition, Syk function required the CD45 transmembrane protein tyrosine phosphatase [22].
  • The complete cDNA sequence of mouse T200 glycoprotein from the pre-B-cell line 70Z/3 has been determined [20].
  • CD45 is a transmembrane phosphotyrosine phosphatase expressed on all nucleated hemopoietic cells [23].
  • However, TCR-induced signaling was not ablated, and significant inositol phosphate and calcium signals were observed in CD45-null thymocytes [23].
  • Here, we report the phenotype of mice with a single point mutation, glutamate 613 to arginine, that inactivates the inhibitory wedge of CD45 [2].
  • These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56(lck) tyrosine kinase phosphorylation sites [24].

Physical interactions of Ptprc

  • To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression [25].
  • The results of our studies showed that in T-cells, CD45-AP is part of a multimolecular complex that includes not only CD45, but also TCR, the CD4 and CD8 coreceptors, and p56(lck) [26].
  • Fyn co-immunoprecipitated with CD45 from differentiating wild-type OPCs in vitro, while CD45-deficient OPCs failed to differentiate [27].
  • Rather, UV radiation selectively activated lymph node B cells, with these cells being larger and expressing higher levels of both anti-major histocompatibility complex II and B220 but not co-stimulatory molecules [28].

Enzymatic interactions of Ptprc


Regulatory relationships of Ptprc


Other interactions of Ptprc

  • The motheaten mutation rescues B cell signaling and development in CD45-deficient mice [15].
  • Therefore, our results support a model in which binding of CD45-AP to inactive CD45 dimers converts them to active monomers [17].
  • Loss of c-kit accompanies B-lineage commitment and acquisition of CD45R by most murine B-lymphocyte precursors [35].
  • Selective regulation of Lyn tyrosine kinase by CD45 in immature B cells [36].
  • CD45 modulates the activity of Src family protein-tyrosine kinases involved at the onset of antigen receptor-mediated signaling by dephosphorylating their regulatory tyrosyl residues [37].

Analytical, diagnostic and therapeutic context of Ptprc


  1. Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro. Murray, L., Martens, C. Cell. Immunol. (1990) [Pubmed]
  2. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Majeti, R., Xu, Z., Parslow, T.G., Olson, J.L., Daikh, D.I., Killeen, N., Weiss, A. Cell (2000) [Pubmed]
  3. Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice. Baker, M., Gamble, J., Tooze, R., Higgins, D., Yang, F.T., O'Brien, P.C., Coleman, N., Pingel, S., Turner, M., Alexander, D.R. EMBO J. (2000) [Pubmed]
  4. Combinations of CD45 isoforms are crucial for immune function and disease. Dawes, R., Petrova, S., Liu, Z., Wraith, D., Beverley, P.C., Tchilian, E.Z. J. Immunol. (2006) [Pubmed]
  5. Reduced expression of CD45 protein-tyrosine phosphatase provides protection against anthrax pathogenesis. Panchal, R.G., Ulrich, R.L., Bradfute, S.B., Lane, D., Ruthel, G., Kenny, T.A., Iversen, P.L., Anderson, A.O., Gussio, R., Raschke, W.C., Bavari, S. J. Biol. Chem. (2009) [Pubmed]
  6. T cell development in mice expressing splice variants of the protein tyrosine phosphatase CD45. Kozieradzki, I., Kündig, T., Kishihara, K., Ong, C.J., Chiu, D., Wallace, V.A., Kawai, K., Timms, E., Ionescu, J., Ohashi, P., Marth, J.D., Mak, T.W., Penninger, J.M. J. Immunol. (1997) [Pubmed]
  7. CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase. Tan, J., Town, T., Mori, T., Wu, Y., Saxe, M., Crawford, F., Mullan, M. J. Neurosci. (2000) [Pubmed]
  8. Protection against 12-O-tetradecanoylphorbol-13-acetate induced skin-hyperplasia and tumor promotion, in a two-stage carcinogenesis mouse model, by the 2,3-dimethyl-6(2-dimethylaminoethyl)-6H-indolo-[2,3-b]quinoxaline analogue of ellipticine. Skarin, T., Rozell, B.L., Bergman, J., Toftgård, R., Möller, L. Chem. Biol. Interact. (1999) [Pubmed]
  9. Flow cytometric patterns in blood from dogs with non-neoplastic and neoplastic hematologic diseases using double labeling for CD18 and CD45. Comazzi, S., Gelain, M.E., Spagnolo, V., Riondato, F., Guglielmino, R., Sartorelli, P. Veterinary clinical pathology / American Society for Veterinary Clinical Pathology. (2006) [Pubmed]
  10. CD45: a critical regulator of signaling thresholds in immune cells. Hermiston, M.L., Xu, Z., Weiss, A. Annu. Rev. Immunol. (2003) [Pubmed]
  11. T-cell-independent antiviral B cell responses in CD45-deficient mice. Bachmann, M.F., Kündig, T.M., Speiser, D.E., McKall-Faienza, K., Kishara, K., Mak, T.W., Ohashi, P.S. Cell. Immunol. (1997) [Pubmed]
  12. Signaling mutations and autoimmunity. Yu, C.C., Mamchak, A.A., DeFranco, A.L. Curr. Dir. Autoimmun. (2003) [Pubmed]
  13. Preliminary characterization of two thymus-dependent xenoantigens from mouse lymphocytes. Trowbridge, I.S., Nilsen-Hamilton, M., Hamilton, R.T., Bevan, M.J. Biochem. J. (1977) [Pubmed]
  14. Defective depletion of CD45-null thymocytes by the Staphylococcus aureus enterotoxin B superantigen. Conroy, L.A., Byth, K.F., Howlett, S., Holmes, N., Alexander, D.R. Immunol. Lett. (1996) [Pubmed]
  15. 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]
  16. A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine production from killing in primary natural killer cells. Huntington, N.D., Xu, Y., Nutt, S.L., Tarlinton, D.M. J. Exp. Med. (2005) [Pubmed]
  17. CD45-associated protein inhibits CD45 dimerization and up-regulates its protein tyrosine phosphatase activity. Takeda, A., Matsuda, A., Paul, R.M., Yaseen, N.R. Blood (2004) [Pubmed]
  18. Characterization of lymphoid tumors induced by a recombinant murine retrovirus carrying the avian v-myc oncogene. Identification of novel (B-lymphoid) tumors in the thymus. Brightman, B.K., Chandy, K.G., Spencer, R.H., Gupta, S., Pattengale, P.K., Fan, H. J. Immunol. (1988) [Pubmed]
  19. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. North, T.E., de Bruijn, M.F., Stacy, T., Talebian, L., Lind, E., Robin, C., Binder, M., Dzierzak, E., Speck, N.A. Immunity (2002) [Pubmed]
  20. B-cell variant of mouse T200 (Ly-5): evidence for alternative mRNA splicing. Thomas, M.L., Reynolds, P.J., Chain, A., Ben-Neriah, Y., Trowbridge, I.S. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  21. Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice. Haudek, S.B., Xia, Y., Huebener, P., Lee, J.M., Carlson, S., Crawford, J.R., Pilling, D., Gomer, R.H., Trial, J., Frangogiannis, N.G., Entman, M.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Restoration of thymocyte development and function in zap-70-/- mice by the Syk protein tyrosine kinase. Gong, Q., White, L., Johnson, R., White, M., Negishi, I., Thomas, M., Chan, A.C. Immunity (1997) [Pubmed]
  23. Aberrant TCR-mediated signaling in CD45-null thymocytes involves dysfunctional regulation of Lck, Fyn, TCR-zeta, and ZAP-70. Stone, J.D., Conroy, L.A., Byth, K.F., Hederer, R.A., Howlett, S., Takemoto, Y., Holmes, N., Alexander, D.R. J. Immunol. (1997) [Pubmed]
  24. The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses. McNeill, L., Salmond, R.J., Cooper, J.C., Carret, C.K., Cassady-Cain, R.L., Roche-Molina, M., Tandon, P., Holmes, N., Alexander, D.R. Immunity (2007) [Pubmed]
  25. Differential T cell receptor-mediated signaling in naive and memory CD4 T cells. Farber, D.L., Acuto, O., Bottomly, K. Eur. J. Immunol. (1997) [Pubmed]
  26. Interactions of CD45-associated protein with the antigen receptor signaling machinery in T-lymphocytes. Veillette, A., Soussou, D., Latour, S., Davidson, D., Gervais, F.G. J. Biol. Chem. (1999) [Pubmed]
  27. Involvement of CD45 in central nervous system myelination. Nakahara, J., Seiwa, C., Tan-Takeuchi, K., Gotoh, M., Kishihara, K., Ogawa, M., Asou, H., Aiso, S. Neurosci. Lett. (2005) [Pubmed]
  28. B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity. Byrne, S.N., Halliday, G.M. J. Invest. Dermatol. (2005) [Pubmed]
  29. The noncatalytic domains of Lck regulate its dephosphorylation by CD45. Lefebvre, D.C., Felberg, J., Cross, J.L., Johnson, P. Biochim. Biophys. Acta (2003) [Pubmed]
  30. Molecular cloning of the CD45-associated 30-kDa protein. Takeda, A., Maizel, A.L., Kitamura, K., Ohta, T., Kimura, S. J. Biol. Chem. (1994) [Pubmed]
  31. Pax7 is necessary and sufficient for the myogenic specification of CD45+:Sca1+ stem cells from injured muscle. Seale, P., Ishibashi, J., Scimè, A., Rudnicki, M.A. PLoS Biol. (2004) [Pubmed]
  32. The CD45 tyrosine phosphatase regulates CD3-induced signal transduction and T cell development in recombinase-deficient mice: restoration of pre-TCR function by active p56(lck). Pingel, S., Baker, M., Turner, M., Holmes, N., Alexander, D.R. Eur. J. Immunol. (1999) [Pubmed]
  33. Peripheral T cells undergoing superantigen-induced apoptosis in vivo express B220 and upregulate Fas and Fas ligand. Renno, T., Hahne, M., Tschopp, J., MacDonald, H.R. J. Exp. Med. (1996) [Pubmed]
  34. Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells. Udagawa, T., Puder, M., Wood, M., Schaefer, B.C., D'Amato, R.J. FASEB J. (2006) [Pubmed]
  35. Loss of c-kit accompanies B-lineage commitment and acquisition of CD45R by most murine B-lymphocyte precursors. Payne, K.J., Medina, K.L., Kincade, P.W. Blood (1999) [Pubmed]
  36. Selective regulation of Lyn tyrosine kinase by CD45 in immature B cells. Katagiri, T., Ogimoto, M., Hasegawa, K., Mizuno, K., Yakura, H. J. Biol. Chem. (1995) [Pubmed]
  37. Interaction between CD45-AP and protein-tyrosine kinases involved in T cell receptor signaling. Motoya, S., Kitamura, K., Matsuda, A., Maizel, A.L., Yamamoto, H., Takeda, A. J. Biol. Chem. (1999) [Pubmed]
  38. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. Tamaki, T., Akatsuka, A., Ando, K., Nakamura, Y., Matsuzawa, H., Hotta, T., Roy, R.R., Edgerton, V.R. J. Cell Biol. (2002) [Pubmed]
  39. Mouse models of hematopoietic engraftment: limitations of transgenic green fluorescent protein strains and a high-performance liquid chromatography approach to analysis of erythroid chimerism. Spangrude, G.J., Cho, S., Guedelhoefer, O., Vanwoerkom, R.C., Fleming, W.H. Stem Cells (2006) [Pubmed]
  40. Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage. Atmaca-Sonmez, P., Li, Y., Yamauchi, Y., Schanie, C.L., Ildstad, S.T., Kaplan, H.J., Enzmann, V. Exp. Eye Res. (2006) [Pubmed]
  41. Cloned natural suppressor cell lines derived from the spleens of neonatal mice. Schwadron, R.B., Gandour, D.M., Strober, S. J. Exp. Med. (1985) [Pubmed]
  42. CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes, and B cell maturation. Byth, K.F., Conroy, L.A., Howlett, S., Smith, A.J., May, J., Alexander, D.R., Holmes, N. J. Exp. Med. (1996) [Pubmed]
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