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Gene Review

PTPRC  -  protein tyrosine phosphatase, receptor...

Homo sapiens

Synonyms: B220, CD45, CD45R, GP180, L-CA, ...
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Disease relevance of PTPRC

  • A point mutation in exon A (C to G transversion at position 77) of human PTPRC (CD45) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients [1].
  • The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that PTPRC could play a role as susceptibility gene not only in MS but also in other autoimmune diseases [1].
  • A deletion in the gene encoding the CD45 antigen in a patient with SCID [2].
  • CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface [3].
  • Consistent with these data, insulin receptor signaling is increased when the CD45-related PTPase LAR is reduced by antisense suppression in a rat hepatoma cell line [4].

Psychiatry related information on PTPRC

  • In addition, loss of CD45 can affect microglia activation in a mouse model for Alzheimer's disease [5].
  • In an examination of T cell expression of these two CD45 isoforms during human development, the RO+RA- "memory" T cells were infrequent in the newborn blood and spleen, but comprised approximately half of the T cells in adult tissues [6].
  • Of the patients with CJD, two with a subacute spongiform encephalopathic type and short-survival periods after onset of the disease showed an increased number of reactive microglia labeled with anti-MHC class II Ag or LCA in the affected cerebral cortex [7].

High impact information on PTPRC

  • Finally, a deficiency of CD45, a critical regulator of signaling thresholds in immune cells, also causes SCID [8].
  • In addition, genetic evidence has demonstrated the requirement of the transmembrane PTPase, CD45, for TCR function [9].
  • In particular, evidence from genetic experiments indicates that CD45 plays a pivotal role in antigen-stimulated proliferation of T lymphocytes and in thymic development [10].
  • CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development [10].
  • CD45 is one of the most abundant leukocyte cell surface glycoproteins and is expressed exclusively upon cells of the hematopoietic system [10].

Chemical compound and disease context of PTPRC


Biological context of PTPRC


Anatomical context of PTPRC

  • CD45, encoded by PTPRC in humans, is the most abundantly expressed protein on the surface of many lymphocytes [19].
  • CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells [20].
  • Association of CD2 and CD45 on human T lymphocytes [21].
  • In this article, Ed Clark and Jeff Ledbetter discuss recent findings in the emerging area of leukocyte cell surface enzymology with emphasis on CD45, a membrane-associated protein tyrosine phosphatase (PTPase)2,3 [22].
  • These transmembrane proteins are selectively sorted in microvesicles because CD28 and CD45, which are highly expressed at the plasma membrane, are not found [23].

Associations of PTPRC with chemical compounds


Physical interactions of PTPRC

  • Moreover, we show that CD26 directly binds to the cytoplasmic domain of CD45 [28].
  • Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its apoptotic signal in T cell lines [29].
  • In contrast, the increase in [Ca2+]i induced by formation of homoaggregates of CD4 was strongly amplified when CD4 was coupled to CD45 [30].
  • We compared the effect of CD45 ligation on signal transduction mediated by the binding of IL2 or anti-CD3 to these two receptors [31].
  • Our results confirm and extend previous observations that CD22 is a sialic acid-binding lectin which interacts with CD45 and other glycoproteins capable of presenting alpha 2,6-linked sialic acid in a manner that promotes high affinity binding [32].

Enzymatic interactions of PTPRC

  • We also showed that phosphorylated JAK1 and JAK3 were directly dephosphorylated by recombinant CD45 in vitro [33].
  • Ezrin was constitutively tyrosine phosphorylated in wild-type and CD45-deficient Jurkat T cells, but not in Lck-deficient cells [34].
  • Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain [25].
  • In contrast, CD45 ligation did not alter the pattern of tyrosine-phosphorylated proteins in "resting" T-cell blasts responding to IL2, except for a mobility shift of a 55 kDa protein and increased phosphorylation of a 112 kDa substrate [31].
  • In addition, phospholipase Cgamma1 (PLCgamma1) and PLCgamma2 were tyrosine phosphorylated upon Ag stimulation in CD45- cells, despite much reduced inositol trisphosphate production and lack of calcium mobilization [35].

Regulatory relationships of PTPRC

  • In Jurkat T cells, betaI spectrin peptides suppress surface recruitment of CD45 and CD3 and abrogate T cell activation [36].
  • In addition, the intracytoplasmic amino acids adjacent to the transmembrane region of LPAP may influence its binding to CD45 [37].
  • Furthermore, we show that the association is increased during T cell activation and that triggering CD45 molecules through discrete epitopes induces the down-modulation of CD100 molecules at the cell surface [38].
  • Anti-CD45 triggering of CD45 significantly inhibited interleukin-4 + anti-CD40-induced switch recombination in a switch recombination vector assay in stably transfected Ramos 2G6 human B cells, as well as Ig epsilon germ-line transcription and Smu-Sepsilon switch recombination in primary human B cells [33].
  • We observed a significant reduction in CXCL12-induced chemotaxis in the CD45-negative Jurkat cell line (J45.01) as compared with the CD45-positive control (JE6.1) cells [26].

Other interactions of PTPRC

  • Using chemical crosslinking techniques, we now show that CD45 is linked to CD2 on the surface of human T lymphocytes [21].
  • The spectrin-ankyrin skeleton controls CD45 surface display and interleukin-2 production [36].
  • Regulation of CD45 engagement by the B-cell receptor CD22 [24].
  • Importantly, aggregation of CD26 by anti-CD26 mAb crosslinking also causes coaggregation of CD45 into rafts [28].
  • By contrast, the CD45 antigens possess protein-tyrosine phosphatase activity within their intracellular domains and are postulated to function by virtue of a regulatory interaction with CD4/CD8:p56lck and its potential substrates [39].

Analytical, diagnostic and therapeutic context of PTPRC


  1. Enhanced frequency of a PTPRC (CD45) exon A mutation (77C-->G) in systemic sclerosis. Schwinzer, R., Witte, T., Hundrieser, J., Ehlers, S., Momot, T., Hunzelmann, N., Krieg, T., Schmidt, R.E., Wonigeit, K. Genes Immun. (2003) [Pubmed]
  2. A deletion in the gene encoding the CD45 antigen in a patient with SCID. Tchilian, E.Z., Wallace, D.L., Wells, R.S., Flower, D.R., Morgan, G., Beverley, P.C. J. Immunol. (2001) [Pubmed]
  3. Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. Pace, K.E., Lee, C., Stewart, P.L., Baum, L.G. J. Immunol. (1999) [Pubmed]
  4. The transmembrane protein-tyrosine phosphatase CD45 is associated with decreased insulin receptor signaling. Kulas, D.T., Freund, G.G., Mooney, R.A. J. Biol. Chem. (1996) [Pubmed]
  5. CD45: new jobs for an old acquaintance. Penninger, J.M., Irie-Sasaki, J., Sasaki, T., Oliveira-dos-Santos, A.J. Nat. Immunol. (2001) [Pubmed]
  6. A novel subpopulation of primed T cells in the human fetus. Byrne, J.A., Stankovic, A.K., Cooper, M.D. J. Immunol. (1994) [Pubmed]
  7. Immunohistochemical study of microglia in the Creutzfeldt-Jakob diseased brain. Sasaki, A., Hirato, J., Nakazato, Y. Acta Neuropathol. (1993) [Pubmed]
  8. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Buckley, R.H. Annu. Rev. Immunol. (2004) [Pubmed]
  9. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Chan, A.C., Desai, D.M., Weiss, A. Annu. Rev. Immunol. (1994) [Pubmed]
  10. CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Trowbridge, I.S., Thomas, M.L. Annu. Rev. Immunol. (1994) [Pubmed]
  11. Protein tyrosine phosphatase receptor-type C exon 4 gene mutation distribution in an Italian multiple sclerosis population. Ballerini, C., Rosati, E., Salvetti, M., Ristori, G., Cannoni, S., Biagioli, T., Massacesi, L., Sorbi, S., Vergelli, M. Neurosci. Lett. (2002) [Pubmed]
  12. Negative regulation of the NFAT1 factor by CD45: implication in HIV-1 long terminal repeat activation. Barbeau, B., Robichaud, G.A., Fortin, J.F., Tremblay, M.J. J. Immunol. (2001) [Pubmed]
  13. HIV-1 gp120-mediated Apoptosis of T Cells Is Regulated by the Membrane Tyrosine Phosphatase CD45. Anand, A.R., Ganju, R.K. J. Biol. Chem. (2006) [Pubmed]
  14. Catalytic domains of the LAR and CD45 protein tyrosine phosphatases from Escherichia coli expression systems: purification and characterization for specificity and mechanism. Cho, H., Ramer, S.E., Itoh, M., Kitas, E., Bannwarth, W., Burn, P., Saito, H., Walsh, C.T. Biochemistry (1992) [Pubmed]
  15. Establishment of a CD45-positive immature plasma cell line from an aggressive multiple myeloma with high serum lactate dehydrogenase. Hata, H., Matsuzaki, H., Sonoki, T., Takemoto, S., Kuribayashi, N., Nagasaki, A., Takatsuki, K. Leukemia (1994) [Pubmed]
  16. Regulatory polymorphisms underlying complex disease traits. Knight, J.C. J. Mol. Med. (2005) [Pubmed]
  17. CD45 variant alleles: possibly increased frequency of a novel exon 4 CD45 polymorphism in HIV seropositive Ugandans. Stanton, T., Boxall, S., Bennett, A., Kaleebu, P., Watera, C., Whitworth, J., French, N., Dawes, R., Hill, A.V., Bodmer, W., Beverley, P.C., Tchilian, E.Z. Immunogenetics (2004) [Pubmed]
  18. Protein tyrosine phosphatase receptor type C polypeptide (PTPRC) on human chromosome band 1q31-->q32 localizes with marker D1S413(1) on a 610-kb yeast artificial chromosome. Goff, L.K., van Soest, S., Timón, M., Tchilian, E., Beverley, P.C. Cytogenet. Cell Genet. (1999) [Pubmed]
  19. Rapid evolution by positive Darwinian selection in the extracellular domain of the abundant lymphocyte protein CD45 in primates. Filip, L.C., Mundy, N.I. Mol. Biol. Evol. (2004) [Pubmed]
  20. CD45 isoform expression in autoimmune myasthenia gravis. Tackenberg, B., Nitschke, M., Willcox, N., Ziegler, A., Nessler, S., Schumm, F., Oertel, W.H., Hemmer, B., Sommer, N. Autoimmunity (2003) [Pubmed]
  21. Association of CD2 and CD45 on human T lymphocytes. Schraven, B., Samstag, Y., Altevogt, P., Meuer, S.C. Nature (1990) [Pubmed]
  22. Leukocyte cell surface enzymology: CD45 (LCA, T200) is a protein tyrosine phosphatase. Clark, E.A., Ledbetter, J.A. Immunol. Today (1989) [Pubmed]
  23. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G., Hivroz, C. J. Immunol. (2002) [Pubmed]
  24. Regulation of CD45 engagement by the B-cell receptor CD22. Sgroi, D., Koretzky, G.A., Stamenkovic, I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  25. Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain. Furukawa, T., Itoh, M., Krueger, N.X., Streuli, M., Saito, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Differential regulation of CXCR4-mediated T-cell chemotaxis and mitogen-activated protein kinase activation by the membrane tyrosine phosphatase, CD45. Fernandis, A.Z., Cherla, R.P., Ganju, R.K. J. Biol. Chem. (2003) [Pubmed]
  27. Physical associations between CD45 and CD4 or CD8 occur as late activation events in antigen receptor-stimulated human T cells. Mittler, R.S., Rankin, B.M., Kiener, P.A. J. Immunol. (1991) [Pubmed]
  28. CD26-mediated signaling for T cell activation occurs in lipid rafts through its association with CD45RO. Ishii, T., Ohnuma, K., Murakami, A., Takasawa, N., Kobayashi, S., Dang, N.H., Schlossman, S.F., Morimoto, C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  29. Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its apoptotic signal in T cell lines. Fajka-Boja, R., Szemes, M., Ion, G., Légrádi, A., Caron, M., Monostori, E. Immunol. Lett. (2002) [Pubmed]
  30. CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells. Ledbetter, J.A., Tonks, N.K., Fischer, E.H., Clark, E.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  31. CD45 ligation in T cells regulates signal transduction through both the interleukin-2 receptor and the CD3/Ti T-cell receptor complex. Gilliland, L.K., Schieven, G.L., Grosmaire, L.S., Damle, N.K., Ledbetter, J.A. Tissue Antigens (1990) [Pubmed]
  32. The B-cell adhesion molecule CD22 is cross-species reactive and recognizes distinct sialoglycoproteins on different functional T-cell sub-populations. Sgroi, D., Stamenkovic, I. Scand. J. Immunol. (1994) [Pubmed]
  33. CD45 controls interleukin-4-mediated IgE class switch recombination in human B cells through its function as a Janus kinase phosphatase. Yamada, T., Zhu, D., Saxon, A., Zhang, K. J. Biol. Chem. (2002) [Pubmed]
  34. Ezrin is a substrate for Lck in T cells. Autero, M., Heiska, L., Rönnstrand, L., Vaheri, A., Gahmberg, C.G., Carpén, O. FEBS Lett. (2003) [Pubmed]
  35. Molecular targets of CD45 in B cell antigen receptor signal transduction. Pao, L.I., Bedzyk, W.D., Persin, C., Cambier, J.C. J. Immunol. (1997) [Pubmed]
  36. The spectrin-ankyrin skeleton controls CD45 surface display and interleukin-2 production. Pradhan, D., Morrow, J. Immunity (2002) [Pubmed]
  37. Identification of the sites of interaction between lymphocyte phosphatase-associated phosphoprotein (LPAP) and CD45. Bruyns, E., Hendricks-Taylor, L.R., Meuer, S., Koretzky, G.A., Schraven, B. J. Biol. Chem. (1995) [Pubmed]
  38. CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion. Herold, C., Elhabazi, A., Bismuth, G., Bensussan, A., Boumsell, L. J. Immunol. (1996) [Pubmed]
  39. Molecular interactions, T-cell subsets and a role of the CD4/CD8:p56lck complex in human T-cell activation. Rudd, C.E., Anderson, P., Morimoto, C., Streuli, M., Schlossman, S.F. Immunol. Rev. (1989) [Pubmed]
  40. Prolonged expression of high molecular mass CD45RA isoform during the differentiation of human progenitor thymocytes to CD3+ cells in vitro. Deans, J.P., Wilkins, J.A., Caixia, S., Pruski, E., Pilarski, L.M. J. Immunol. (1991) [Pubmed]
  41. CD45 modulates T cell receptor/CD3-induced activation of human thymocytes via regulation of tyrosine phosphorylation. Turka, L.A., Kanner, S.B., Schieven, G.L., Thompson, C.B., Ledbetter, J.A. Eur. J. Immunol. (1992) [Pubmed]
  42. Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocyte-common antigen (CD45). Lazarovits, A.I., Poppema, S., White, M.J., Karsh, J. Transplantation (1992) [Pubmed]
  43. Characterization of epithelial cell shedding from human small intestine. Bullen, T.F., Forrest, S., Campbell, F., Dodson, A.R., Hershman, M.J., Pritchard, D.M., Turner, J.R., Montrose, M.H., Watson, A.J. Lab. Invest. (2006) [Pubmed]
  44. A study on CD45 isoform expression during T-cell development and selection events in the human thymus. Fukuhara, K., Okumura, M., Shiono, H., Inoue, M., Kadota, Y., Miyoshi, S., Matsuda, H. Hum. Immunol. (2002) [Pubmed]
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