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Ptprc  -  protein tyrosine phosphatase, receptor...

Rattus norvegicus

Synonyms: CD45, L-CA, Lca, Leukocyte common antigen, RT7, ...
 
 
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Disease relevance of Ptprc

 

High impact information on Ptprc

  • Here we investigated the role of a point mutation in the gene (PTPRC) encoding protein-tyrosine phosphatase, receptor-type C (also known as CD45) in the heterozygous state in the development of MS [1].
  • The leukocyte-common antigen (L-CA or T200) includes a family of lymphoid and myeloid cell surface glycoproteins with apparent molecular weights from 180,000 to 240,000 [6].
  • Using a monoclonal antibody that detects a donor-specific CD45 allotype (RT7a), we selectively depleted donor leukocytes at different times after transplantation (days 0 or 18) [7].
  • T lymphocytes express multiple forms of the leukocyte common antigen CD45, transcribed by alternative usage of leukocyte-common antigen exons 4-6 [8].
  • CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify "naive" (CD45Rhigh) and "memory" (CD45Rlow) subsets [9].
 

Biological context of Ptprc

  • Forms of L-CA which differ in their apparent Mr, antigenicity and glycosylation are expressed on different lymphocyte types [10].
  • Two phosphatase domains are encoded by 16 exons in a genomic organization similar to those in RPRPalpha, RPTPgamma, and Ptprc genes [11].
  • The RT7 promoter contains a TATA box as well as sequences with homology to binding sites for a number of transcription factors [12].
  • In addition, major histocompatibility complex (MHC)-congenic BM transplantation making use of a diallelic polymorphism (RT7(a)/RT7(b)) of rat CD45 was applied [13].
  • Relative to microglia from the normal CNS, those from the GvHD-affected CNS exhibited a 5-fold up-regulation of characteristically low CD45, MHC class II expression was increased 10- to 20-fold, and microglial cell recoveries were enhanced substantially [14].
 

Anatomical context of Ptprc

  • Similar CD45 mRNA levels were found in acinar cells and leukocytes (positive control) [15].
  • Using irradiation chimeras, we show that resident microglia respond to inflammation by upregulating CD45, CD4, and MHC class I molecules with a minority of these cells increasing their expression of MHC class II molecules [16].
  • To investigate the regulation of the RT7 promoter we developed an active in vitro transcription system derived from rat seminiferous epithelium, which, in contrast to total testis, consists mostly of male germ cells [12].
  • In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7) antibody [13].
  • Clustering is stimulated by cross-linking MHC class II (whole mAb or F(ab')2) on DC or B cells or Thy-1 on DC, but not MHC class I, CD45, or CD44 [17].
 

Associations of Ptprc with chemical compounds

  • Lymphocyte specific heterogeneity in the rat leucocyte common antigen (T200) is due to differences in polypeptide sequences near the NH2-terminus [10].
  • The leucocyte-common antigen (L-CA) from rat thymocytes is a cell surface glycoprotein of 180 000 apparent mol. wt. with an 80-kd cytoplasmic domain [18].
  • The two partially purified MBP kinases were inactivated by the protein tyrosine phosphatase CD45 or by protein phosphatase 2a (PP-2a) [19].
  • The cytolytic activity of the CD45-negative cells could be stimulated pharmacologically by ionomycin and PMA, which, when added to the cytotoxicity assays, induced killing of tumor targets [20].
  • Injured cortex from cyclosporine-treated animals demonstrated increased numbers of T helper and B lymphocytes, macrophages, and cells bearing LCA [21].
 

Other interactions of Ptprc

 

Analytical, diagnostic and therapeutic context of Ptprc

  • In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution [24].
  • Each of these lacked cell-surface expression of CD45 and did not have detectable transcripts for CD45 on Northern blot analysis [20].
  • DNAase I footprint analysis and gel-retardation assays showed binding of a novel testis-specific nuclear factor to the rat testis c-mos promoter at a site homologous to the testis-specific cis-acting element identified in the promoter of the RT7 gene, which is specifically expressed in haploid male germ cells [25].
  • Immunofluorescent dual labeling of NIL cells for flow cytometry revealed that greater than 95% of the cells did not stain for CD11b/c (common epitope found on monocytes, granulocytes, and macrophages) or CD45 (leukocyte common antigen) [26].
  • CD45 immunohistochemistry was performed to confirm that ConA-stained cells within the vasculature were leukocytes [27].

References

  1. A point mutation in PTPRC is associated with the development of multiple sclerosis. Jacobsen, M., Schweer, D., Ziegler, A., Gaber, R., Schock, S., Schwinzer, R., Wonigeit, K., Lindert, R.B., Kantarci, O., Schaefer-Klein, J., Schipper, H.I., Oertel, W.H., Heidenreich, F., Weinshenker, B.G., Sommer, N., Hemmer, B. Nat. Genet. (2000) [Pubmed]
  2. Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: a model to study marginal organ donors. van der Hoeven, J.A., Ploeg, R.J., Postema, F., Molema, I., de Vos, P., Girbes, A.R., van Suylichem, P.T., van Schilfgaarde, R., Ter Horst, G.J. Transplantation (1999) [Pubmed]
  3. Role of Angiotensin-converting enzyme and neutral endopeptidase in flow-dependent remodeling. Korshunov, V.A., Massett, M.P., Carey, R.M., Berk, B.C. J. Vasc. Res. (2004) [Pubmed]
  4. CD45 monoclonal antibody-mediated cytolysis of human NK and T lymphoma cells. Wulf, G.G., Boehnke, A., Chapuy, B., Glass, B., Hemmerlein, B., Schroers, R., Brenner, M.K., Truemper, L. Haematologica (2006) [Pubmed]
  5. Experimental esophageal carcinogenesis: technical standardization and results. Sallet, J.A., Zilberstein, B., Andreollo, N.A., Eshkenazy, R., Pajecki, D. Dis. Esophagus (2002) [Pubmed]
  6. Evidence from cDNA clones that the rat leukocyte-common antigen (T200) spans the lipid bilayer and contains a cytoplasmic domain of 80,000 Mr. Thomas, M.L., Barclay, A.N., Gagnon, J., Williams, A.F. Cell (1985) [Pubmed]
  7. The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat. Ko, S., Deiwick, A., Jäger, M.D., Dinkel, A., Rohde, F., Fischer, R., Tsui, T.Y., Rittmann, K.L., Wonigeit, K., Schlitt, H.J. Nat. Med. (1999) [Pubmed]
  8. Interconversion of CD45R subsets of CD4 T cells in vivo. Bell, E.B., Sparshott, S.M. Nature (1990) [Pubmed]
  9. CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen. Bunce, C., Bell, E.B. J. Exp. Med. (1997) [Pubmed]
  10. Lymphocyte specific heterogeneity in the rat leucocyte common antigen (T200) is due to differences in polypeptide sequences near the NH2-terminus. Barclay, A.N., Jackson, D.I., Willis, A.C., Williams, A.F. EMBO J. (1987) [Pubmed]
  11. Rat osteotesticular phosphatase gene (Esp): genomic structure and chromosome location. Lathrop, W., Jordan, J., Eustice, D., Chen, D. Mamm. Genome (1999) [Pubmed]
  12. Factors involved in regulation of the RT7 promoter in a male germ cell-derived in vitro transcription system. van der Hoorn, F.A., Tarnasky, H.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  13. In vivo depletion of hematopoietic stem cells in the rat by an anti-CD45 (RT7) antibody. Dahlke, M.H., Lauth, O.S., Jäger, M.D., Roeseler, T., Timrott, K., Jackobs, S., Neipp, M., Wonigeit, K., Schlitt, H.J. Blood (2002) [Pubmed]
  14. Central nervous system microglial cell activation and proliferation follows direct interaction with tissue-infiltrating T cell blasts. Sedgwick, J.D., Ford, A.L., Foulcher, E., Airriess, R. J. Immunol. (1998) [Pubmed]
  15. CD45 expression on rat acinar cells: involvement in pro-inflammatory cytokine production. De Dios, I., Ramudo, L., Alonso, J.R., Recio, J.S., Garcia-Montero, A.C., Manso, M.A. FEBS Lett. (2005) [Pubmed]
  16. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Sedgwick, J.D., Schwender, S., Imrich, H., Dörries, R., Butcher, G.W., ter Meulen, V. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  17. Dendritic cells and resting B cells form clusters in vitro and in vivo: T cell independence, partial LFA-1 dependence, and regulation by cross-linking surface molecules. Kushnir, N., Liu, L., MacPherson, G.G. J. Immunol. (1998) [Pubmed]
  18. Visualisation by low-angle shadowing of the leucocyte-common antigen. A major cell surface glycoprotein of lymphocytes. Woollett, G.R., Williams, A.F., Shotton, D.M. EMBO J. (1985) [Pubmed]
  19. Okadaic acid mimics the action of insulin in stimulating protein kinase activity in isolated adipocytes. The role of protein phosphatase 2a in attenuation of the signal. Haystead, T.A., Weiel, J.E., Litchfield, D.W., Tsukitani, Y., Fischer, E.H., Krebs, E.G. J. Biol. Chem. (1990) [Pubmed]
  20. CD45-negative mutants of a rat natural killer cell line fail to lyse tumor target cells. Bell, G.M., Dethloff, G.M., Imboden, J.B. J. Immunol. (1993) [Pubmed]
  21. Characterization of the interstitial cellular infiltrate in experimental chronic cyclosporine nephropathy. Gillum, D.M., Truong, L., Tasby, J. Transplantation (1990) [Pubmed]
  22. Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages. Johansson, A., Lundborg, M., Sköld, C.M., Lundahl, J., Tornling, G., Eklund, A., Camner, P. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  23. Organ-specific maturation of the major histocompatibility antigens in rats. Metzger, R., Parasta, A., Joppich, I., Till, H. Pediatr. Surg. Int. (2002) [Pubmed]
  24. Effect of graft perfusion with two CD45 monoclonal antibodies on incidence of kidney allograft rejection. Brewer, Y., Palmer, A., Taube, D., Welsh, K., Bewick, M., Bindon, C., Hale, G., Waldmann, H., Dische, F., Parsons, V. Lancet (1989) [Pubmed]
  25. Identification of the testis c-mos promoter: specific activity in a seminiferous tubule-derived extract and binding of a testis-specific nuclear factor. van der Hoorn, F.A. Oncogene (1992) [Pubmed]
  26. Neurointermediate pituitary lobe cells synthesize and release interleukin-6 in vitro: effects of lipopolysaccharide and interleukin-1 beta. Spangelo, B.L., deHoll, P.D., Kalabay, L., Bond, B.R., Arnaud, P. Endocrinology (1994) [Pubmed]
  27. VEGF164 is proinflammatory in the diabetic retina. Ishida, S., Usui, T., Yamashiro, K., Kaji, Y., Ahmed, E., Carrasquillo, K.G., Amano, S., Hida, T., Oguchi, Y., Adamis, A.P. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
 
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