Gene Symbol: CD247
Description: CD247 molecule
Alias: CD3-ZETA, CD3H, CD3Q, CD3Z, IMD25, T3Z, TCRZ, T-cell surface glycoprotein CD3 zeta chain, CD247 antigen, zeta subunit, CD3Z antigen, zeta polypeptide (TiT3 complex), CD3zeta chain, T-cell antigen receptor complex, zeta subunit of CD3, T-cell receptor T3 zeta chain, TCR zeta chain
Species: human
Products:     CD247

Top Publications

  1. Chowdhury B, Tsokos C, Krishnan S, Robertson J, Fisher C, Warke R, et al. Decreased stability and translation of T cell receptor zeta mRNA with an alternatively spliced 3'-untranslated region contribute to zeta chain down-regulation in patients with systemic lupus erythematosus. J Biol Chem. 2005;280:18959-66 pubmed
    ..Taken together our findings suggest that nucleotides 672-1233 bp of TCR zeta 3' UTR play a critical role in its stability and also have elements required for the translational regulation of TCR zeta chain expression in human T cells.
  2. Iwashima M, Irving B, van Oers N, Chan A, Weiss A. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science. 1994;263:1136-9 pubmed
    ..Thus, TCR signal transduction is initiated by the sequential interaction of two PTKs with TCR ARAMs. ..
  3. Li Y, He X, Schembri King J, Jakes S, Hayashi J. Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation. J Immunol. 2000;164:5199-206 pubmed
    ..The overexpression of Lnk in Jurkat cells led to an inhibition of anti-CD3 mediated NF-AT-Luc activation. Our study reveals a potentially new mechanism of T cell-negative regulation. ..
  4. Gil D, Schamel W, Montoya M, Sanchez Madrid F, Alarcon B. Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation. Cell. 2002;109:901-12 pubmed
    ..Finally, by interfering with Nck-CD3 epsilon association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation. ..
  5. Sigalov A, Aivazian D, Stern L. Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain and of other proteins containing the immunoreceptor tyrosine-based activation motif. Biochemistry. 2004;43:2049-61 pubmed
    ..Phosphorylation of zeta(cyt) and FcepsilonRIgamma(cyt) does not significantly alter their oligomerization behavior. The implications of these results for transmembrane signaling and cellular activation by immune receptors are discussed. ..
  6. Radstake T, Gorlova O, Rueda B, Martin J, Alizadeh B, Palomino Morales R, et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat Genet. 2010;42:426-9 pubmed publisher
    ..individuals with SSc (cases) and 4,569 controls) identified a new susceptibility locus for systemic sclerosis at CD247 (1q22-23, rs2056626, P = 2.09 x 10(-7) in the discovery samples, P = 3.39 x 10(-9) in the combined analysis)...
  7. Zhernakova A, Stahl E, Trynka G, Raychaudhuri S, Festen E, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 2011;7:e1002004 pubmed publisher
    ..2 × 10(-12)), rs864537 near CD247 (P(combined)?=? 2.2 × 10(-11)), rs2298428 near UBE2L3 (P(combined)?=? 2...
  8. Jensen J, Hou D, Ramsburg M, Taylor A, Dean M, Weissman A. Organization of the human T cell receptor zeta/eta gene and its genetic linkage to the Fc gamma RII-Fc gamma RIII gene cluster. J Immunol. 1992;148:2563-71 pubmed
    ..Surprisingly, translation of this region into protein results in a structure that is markedly divergent from its murine counterpart. This finding has important implications regarding the potential role of eta in T cell function. ..
  9. San José E, Sahuquillo A, Bragado R, Alarcon B. Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. Evidence for a double TCR heterodimer model. Eur J Immunol. 1998;28:12-21 pubmed
    ..These dimers assemble with TCR alpha and TCR beta chains, and finally, the CD3 zeta homodimer is added to allow export of the full complex from the ER...

More Information

Publications153 found, 100 shown here

  1. Bruyns E, Marie Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, et al. T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane. J Exp Med. 1998;188:561-75 pubmed
    ..Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR. ..
  2. Xu X, Laffert B, Screaton G, Kraft M, Wolf D, Kolanus W, et al. Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. J Exp Med. 1999;189:1489-96 pubmed
    ..through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent ..
  3. Greenway A, Holloway G, McPhee D, Ellis P, Cornall A, Lidman M. HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication. J Biosci. 2003;28:323-35 pubmed
  4. Gorman C, Russell A, Zhang Z, Cunninghame Graham D, Cope A, Vyse T. Polymorphisms in the CD3Z gene influence TCRzeta expression in systemic lupus erythematosus patients and healthy controls. J Immunol. 2008;180:1060-70 pubmed
    TCRzeta (CD247) functions as an amplification module in the TCR signaling cascade and is essential for assembly and surface expression of the TCR/CD3 complex...
  5. Kirchhoff F, Schindler M, Specht A, Arhel N, Munch J. Role of Nef in primate lentiviral immunopathogenesis. Cell Mol Life Sci. 2008;65:2621-36 pubmed publisher
    ..This evolutionary loss of a specific Nef function may contribute to the high virulence of HIV-1 in humans. ..
  6. Moulton V, Kyttaris V, Juang Y, Chowdhury B, Tsokos G. The RNA-stabilizing protein HuR regulates the expression of zeta chain of the human T cell receptor-associated CD3 complex. J Biol Chem. 2008;283:20037-44 pubmed publisher
    ..however, the molecular mechanisms involved in the deficient expression of the T cell receptor-associated CD3zeta chain in SLE are not clear...
  7. Aviles D, Vehaskari M, Culotta K, Manning J, Ochoa A, Zea A. T cell CD3 receptor zeta (TCRzeta)-chain expression in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2009;24:769-73 pubmed publisher
    ..Therefore, a decreased expression of the TCRzeta chain may explain the abnormal function of T cells in patients with INS, and it may also contribute to the increased risk for infections seen in these patients. ..
  8. Warchoł T, Piotrowski P, Lianeri M, Cieslak D, Wudarski M, Hrycaj P, et al. The CD3Z 844 T>A polymorphism within the 3'-UTR of CD3Z confers increased risk of incidence of systemic lupus erythematosus. Tissue Antigens. 2009;74:68-72 pubmed publisher
    Recently, a family-based association analysis showed that the haplotype carrying a low expression of the variant CD3Z 844 T>A (rs1052231) polymorphism located in the 3'-untranslated region of CD3Z predisposes to systemic lupus ..
  9. Moulton V, Tsokos G. Alternative splicing factor/splicing factor 2 regulates the expression of the zeta subunit of the human T cell receptor-associated CD3 complex. J Biol Chem. 2010;285:12490-6 pubmed publisher
    T cells from patients with systemic lupus erythematosus express decreased levels of the T cell receptor-associated CD3 zeta chain, a feature directly linked to their aberrant function...
  10. Li R, Yang W, Zhang J, Hirankarn N, Pan H, Mok C, et al. Association of CD247 with systemic lupus erythematosus in Asian populations. Lupus. 2012;21:75-83 pubmed publisher
    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is ..
  11. Isakov N, Wange R, Burgess W, Watts J, Aebersold R, Samelson L. ZAP-70 binding specificity to T cell receptor tyrosine-based activation motifs: the tandem SH2 domains of ZAP-70 bind distinct tyrosine-based activation motifs with varying affinity. J Exp Med. 1995;181:375-80 pubmed
    ..SH2 domains of ZAP-70, and soluble synthetic peptides with the sequence of the cytoplasmic region of the TCR zeta chain (TCR zeta cyt) or individual TCR zeta and CD3 epsilon TAM motifs...
  12. Chan A, van Oers N, Tran A, Turka L, Law C, Ryan J, et al. Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 1994;152:4758-66 pubmed
    ..Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development. ..
  13. Díaz Benítez C, Navarro Fuentes K, Flores Sosa J, Juárez Díaz J, Uribe Salas F, Román Basaure E, et al. CD3zeta expression and T cell proliferation are inhibited by TGF-beta1 and IL-10 in cervical cancer patients. J Clin Immunol. 2009;29:532-44 pubmed publisher
    ..Experiments with T cells from healthy donors in the presence TGF-beta1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression. ..
  14. Gorlova O, Martin J, Rueda B, Koeleman B, Ying J, Teruel M, et al. Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy. PLoS Genet. 2011;7:e1002178 pubmed publisher
    ..Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc. ..
  15. Eldor R, Klieger Y, Sade Feldman M, Vaknin I, Varfolomeev I, Fuchs C, et al. CD247, a novel T cell-derived diagnostic and prognostic biomarker for detecting disease progression and severity in patients with type 2 diabetes. Diabetes Care. 2015;38:113-8 pubmed publisher
    We have previously shown that chronic inflammation results in immunosuppression associated with CD247 downregulation in T lymphocytes. Type 2 diabetes mellitus (T2DM) is known to be associated with chronic inflammation...
  16. Carmona F, Onat A, Fernández Aranguren T, Serrano Fernández A, Robledo G, Direskeneli H, et al. Analysis of Systemic Sclerosis-associated Genes in a Turkish Population. J Rheumatol. 2016;43:1376-9 pubmed publisher
    ..controls from Turkey genotyped for the most relevant SSc genetic markers (IRF5-rs10488631, STAT4-rs3821236, CD247-rs2056626, DNASE1L3-rs35677470, IL12A-rs77583790, and ATG5-rs9373839)...
  17. da Silva A, Yamamoto M, Zalvan C, Rudd C. Engagement of the TcR/CD3 complex stimulates p59fyn(T) activity: detection of associated proteins at 72 and 120-130 kD. Mol Immunol. 1992;29:1417-25 pubmed
    ..Stimulation of fyn activity implicates this kinase as a mediator of the tyrosine phosphorylation events originating from the TcR/CD3 complex. ..
  18. Torres J, Briggs J, Arkin I. Convergence of experimental, computational and evolutionary approaches predicts the presence of a tetrameric form for CD3-zeta. J Mol Biol. 2002;316:375-84 pubmed
    ..These results show that both the known dimeric and the so far undetected tetrameric form may be of functional importance in the cell. ..
  19. Gorska M, Stafford S, Cen O, Sur S, Alam R. Unc119, a novel activator of Lck/Fyn, is essential for T cell activation. J Exp Med. 2004;199:369-79 pubmed
    ..Reconstitution of cells with Unc119 reverses the signaling and functional outcome. Thus, Unc119 is a receptor-associated activator of Src-type kinases. It provides a novel mechanism of signal generation in the TCR complex. ..
  20. Lu X, Chen S, Yang L, Zha X, Yang X, Li Y. The expression pattern of CD3 chain genes in fetal/maternal interface. Hematology. 2011;16:185-9 pubmed publisher
    ..In conclusion, the present study characterized the expression pattern of CD3-gamma, -delta, -epsilon and -zeta chain genes from placenta, which contributes to further understanding of the features of T-cell immune status in placenta. ..
  21. Li B, Liu S, Niu Y, Fang S, Wu X, Yu Z, et al. Altered expression of the TCR signaling related genes CD3 and Fc?RI? in patients with aplastic anemia. J Hematol Oncol. 2012;5:6 pubmed publisher
    ..To our knowledge, this is the first report of the CD3?, CD3?, CD3?, CD3? and Fc?RI? gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA. ..
  22. Vettermann C, Victor H, Sun Y, Plewa C, Gupta S. A signaling-enhanced chimeric receptor to activate the ICOS pathway in T cells. J Immunol Methods. 2015;424:14-9 pubmed publisher
    ..ICOS-CD3) consisting of full-length human ICOS fused at its C-terminal end to the cytoplasmic domain of human CD3 zeta. When engaged by B7RP1, ICOS-CD3 initiated signaling independently of TCR costimulation and induced substantially ..
  23. Blázquez Moreno A, Pérez Portilla A, Agúndez Llaca M, Dukovska D, Vales Gomez M, Aydogmus C, et al. Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes. Blood. 2017;130:1205-1208 pubmed publisher
    ..Here, detailed analyses of spontaneously arising somatic mutations that recover CD247, and thus TCR expression, in a newly identified CD247-deficient patient are described...
  24. Han J, Chen M, Wang Y, Gong B, Zhuang T, Liang L, et al. Identification of Biomarkers Based on Differentially Expressed Genes in Papillary Thyroid Carcinoma. Sci Rep. 2018;8:9912 pubmed publisher
    ..Finally, four newly discovered genes, COMP, COL3A1, ZAP70, and CD247, were found to be related with PTC clinical phenotypes, and were confirmed by Spearman's correlation analyses in ..
  25. Jensen J, Cenciarelli C, Hou D, Rellahan B, Dean M, Weissman A. T cell antigen receptor-eta subunit. Low levels of expression and limited cross-species conservation. J Immunol. 1993;150:122-30 pubmed
  26. Tomita K, Saijo K, Yamasaki S, Iida T, Nakatsu F, Arase H, et al. Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex. J Biol Chem. 2001;276:25378-85 pubmed
    ..These results suggest that Jak3 plays a role not only in cell growth but also in T cell activation and represents cross-talk of a signaling molecule between TCR and growth signals. ..
  27. Fackler O, Wolf D, Weber H, Laffert B, D Aloja P, Schuler Thurner B, et al. A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells. Curr Biol. 2001;11:1294-9 pubmed
    ..Our report suggests that functionally and conformationally distinct Nef isoforms modulate HIV replication on the interaction level with the TCR-signaling environment once the virus enters the T cell compartment. ..
  28. Peng S. Altered T and B lymphocyte signaling pathways in lupus. Autoimmun Rev. 2009;8:179-83 pubmed publisher
    ..This review focuses on recently elucidated signaling abnormalities currently thought to be intrinsic to T and/or B cells in human SLE. ..
  29. Wang Y, Zhuang Q, Hu Z, Lan R, Zhou S. [Effects of B7-H1 blockade on biologic activity of CD3AK cells in vitro]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009;25:671-3 pubmed
    ..It can also improve the antitumor immunity mediated by CD3AK cells. The manipulation of B7-H1 may become a beneficial target for immunotherapy in tumors. ..
  30. Sharif R, Mayes M, Tan F, Gorlova O, Hummers L, Shah A, et al. IRF5 polymorphism predicts prognosis in patients with systemic sclerosis. Ann Rheum Dis. 2012;71:1197-202 pubmed publisher
    ..Five single nucleotide polymorphisms, IRF5 (rs10488631, rs12537284, rs4728142), STAT4 (rs3821236), CD247 (rs2056626) reached genome-wide significance in the SSc-GWAS and were examined in the current study. Overall, 15...
  31. Blázquez Moreno A, Park S, Im W, Call M, Call M, Reyburn H. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. Proc Natl Acad Sci U S A. 2017;114:E5645-E5654 pubmed publisher
    Many activating immunoreceptors associate with signaling adaptor molecules like Fc?R1? or CD247. Fc?R1? and CD247 share high sequence homology and form disulphide-linked homodimers that contain a pair of acidic aspartic acid residues in ..
  32. Tucek C, Godfrey D, Boyd R. Five novel antigens illustrate shared phenotype between mouse thymic stromal cells, thymocytes, and peripheral lymphocytes. Int Immunol. 1992;4:1021-30 pubmed
    ..These findings may be of importance in the delineation of intercellular communications within the thymus and emphasize the integrated nature of the microenvironment in this organ. ..
  33. Verhagen A, Schraven B, Wild M, Wallich R, Meuer S. Differential interaction of the CD2 extracellular and intracellular domains with the tyrosine phosphatase CD45 and the zeta chain of the TCR/CD3/zeta complex. Eur J Immunol. 1996;26:2841-9 pubmed
    ..This study suggests that the CD2 extracellular and intracellular domains are differentially involved in regulating T cell activation through interaction with the tyrosine phosphatase CD45 and the zeta chain of the TCR/CD3/zeta complex. ..
  34. La Face D, Couture C, Anderson K, Shih G, Alexander J, Sette A, et al. Differential T cell signaling induced by antagonist peptide-MHC complexes and the associated phenotypic responses. J Immunol. 1997;158:2057-64 pubmed
    ..We show that antagonist peptides do not cause TCR down-modulation. This failure may represent a mechanism by which antagonists inhibit antigen-mediated stimulation of T cells. ..
  35. Sigalov A, AIVAZIAN D, Uversky V, Stern L. Lipid-binding activity of intrinsically unstructured cytoplasmic domains of multichain immune recognition receptor signaling subunits. Biochemistry. 2006;45:15731-9 pubmed
    ..The implications of these results for transmembrane signal transduction by immune receptors are discussed. ..
  36. Banning C, Votteler J, Hoffmann D, Koppensteiner H, Warmer M, Reimer R, et al. A flow cytometry-based FRET assay to identify and analyse protein-protein interactions in living cells. PLoS ONE. 2010;5:e9344 pubmed publisher
  37. Condomines M, Arnason J, Benjamin R, Gunset G, Plotkin J, Sadelain M. Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition. PLoS ONE. 2015;10:e0130518 pubmed publisher
    ..We investigated whether T cells expressing an anti-CD19, CD3 zeta and CD28-based CAR (19-28z) displayed the same proliferation and anti-tumor abilities than T cells expressing a ..
  38. Ma Q, Garber H, Lu S, He H, Tallis E, Ding X, et al. A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells. Cytotherapy. 2016;18:985-94 pubmed publisher
    ..CAR (h8F4-CAR-T cells) containing the scFv of h8F4 fused to the intracellular signaling endo-domain of CD3 zeta chain through the transmembrane and intracellular costimulatory domain of CD28...
  39. Tsou P, Sawalha A. Unfolding the pathogenesis of scleroderma through genomics and epigenomics. J Autoimmun. 2017;83:73-94 pubmed publisher
    ..Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 ..
  40. Han Y, Xie W, Song D, Powell D. Control of triple-negative breast cancer using ex vivo self-enriched, costimulated NKG2D CAR T cells. J Hematol Oncol. 2018;11:92 pubmed publisher
    ..domain of human NKG2D that binds various NKG2DLs, fused to signaling domains derived from T cell receptor CD3 zeta alone or with CD27 or 4-1BB (CD137) costimulatory domain...
  41. Koning F, Maloy W, Coligan J. The implications of subunit interactions for the structure of the T cell receptor-CD3 complex. Eur J Immunol. 1990;20:299-305 pubmed
    ..The data further indicate that gamma epsilon and delta epsilon complexes interact directly with the TcR chains. Based on the observations a model for the structure of the TcR-CD3 is presented and discussed. ..
  42. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Higashi H, Iwashige H, et al. CD3-zetachain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients. Cancer. 2002;94:1437-42 pubmed
    Impaired or reduced CD3 zeta chain (CD3-zeta) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response...
  43. Serrador J, Cabrero J, Sancho D, Mittelbrunn M, Urzainqui A, Sanchez Madrid F. HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity. 2004;20:417-28 pubmed
    ..Our results underscore the key role for HDAC6 in the organization of the immune synapse and the antigen-specific reorientation of the MTOC...
  44. García Navas R, Munder M, Mollinedo F. Depletion of L-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes. Autophagy. 2012;8:1557-76 pubmed publisher
    ..Here we have found that L-Arg depletion inhibited expression of different membrane antigens, including CD247 (CD3ζ), and led to an ER stress response, as well as cell cycle arrest at G(0)/G(1) in both human Jurkat and ..
  45. Pace M, Graf E, Agosto L, Mexas A, Male F, Brady T, et al. Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 2012;8:e1002818 pubmed publisher
    ..These results have implications for therapies targeting the latent reservoir and suggest that some latent cells could be cleared by a robust immune response. ..
  46. Fernández Arenas E, Calleja E, Martinez Martin N, Gharbi S, Navajas R, García Medel N, et al. ?-Arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism. EMBO J. 2014;33:559-77 pubmed publisher
    ..This receptor crosstalk mechanism is critical to sustain the TCR signal. ..
  47. Krepsova E, Tycova I, Sekerkova A, Wohlfahrt P, Hrubá P, Striz I, et al. Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance. BMC Nephrol. 2015;16:146 pubmed publisher
    ..The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the ..
  48. Chairta P, Nicolaou P, Christodoulou K. Genomic and genetic studies of systemic sclerosis: A systematic review. Hum Immunol. 2017;78:153-165 pubmed publisher
    ..showed that particular alleles in the HLA-DRB1, HLA-DQB1, HLA-DQA1, HLA-DPB1 genes and variants in STAT4, IRF5 and CD247 are frequently associated with SSc...
  49. Rowe J, Delmonte O, Keles S, Stadinski B, Dobbs A, Henderson L, et al. Patients with CD3G mutations reveal a role for human CD3γ in Treg diversity and suppressive function. Blood. 2018;: pubmed publisher
    ..In humans, CD3D, CD3E, and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to ..
  50. Welsh M, Songyang Z, Frantz J, Trub T, Reedquist K, Karlsson T, et al. Stimulation through the T cell receptor leads to interactions between SHB and several signaling proteins. Oncogene. 1998;16:891-901 pubmed
    ..Together, our results show three distinct domains of Shb all participate in the formulation of multimeric signaling complexes in activated T cells. These results indicate that the Shb protein functions in T cell receptor signaling. ..
  51. Rodriguez P, Zea A, Culotta K, Zabaleta J, Ochoa J, Ochoa A. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem. 2002;277:21123-9 pubmed
    ..Therefore, the regulation of L-Arg concentration in the microenvironment could represent an important mechanism to modulate the expression of CD3zeta and the T cell receptor and consequently of T cell function. ..
  52. Lee E, Kim M, Kim H, Kang H, Kim H, Min S, et al. CD3 and CD20 Immunohistochemical Staining Patterns of Bone Marrow-Infiltrating Malignant Lymphoma Cells. Ann Clin Lab Sci. 2017;47:136-143 pubmed
    ..Thus, heterogeneous immunohistochemical staining patterns (particularly in B lineage lymphomas) may signify malignant lymphoma cell infiltration into the BM. ..
  53. Woodward J, Bayer A, Chavin K, Boleza K, Baliga P. Anti-transferrin receptor monoclonal antibody: a novel immunosuppressant. Transplantation. 1998;65:6-9 pubmed
    ..Since transferrin receptor is physically associated with the CD3 zeta-chain, blockade of transferrin receptor has the potential to interfere with the T-cell signals important in ..
  54. Dar A, Pradhan T, Kulkarni D, Shah S, Rao K, Chaukar D, et al. Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer. Immunology. 2016;147:251-64 pubmed publisher
    ..Collectively these results show that OAS2 leads to impairment in CD3-ζ chain expression, so offering an explanation that might be applicable to the CD3-ζ chain deficiency observed in cancer and diverse disease conditions. ..
  55. Hristova M, Kamenarska Z, Dzhebir G, Kaneva R, Vinkov A, Mitev V, et al. The Role of CD247 Polymorphisms in Bulgarian Patients with Systemic Lupus Erythematosus. Acta Dermatovenerol Croat. 2017;25:267-270 pubmed
    ..Recent evidence suggests that this deficiency may be due to polymorphisms in the CD247 gene...
  56. zur Hausen J, Burn P, Amrein K. Co-localization of Fyn with CD3 complex, CD45 or CD28 depends on different mechanisms. Eur J Immunol. 1997;27:2643-9 pubmed
    ..CD28 co-localizes with Fyn molecules that contain the N terminus and a functional SH2 domain. These results suggest that Fyn association with the TCR-CD3 complex, CD45 and CD28 is mediated by different molecular mechanisms. ..
  57. Li C. Therapeutic biology: checkpoint pathway activation therapy, HIV Tat, and transkingdom RNA interference. J Cell Physiol. 2006;209:695-700 pubmed
    ..The third example describes transkingdom RNA interference and its application in the investigational and therapeutic silencing of disease genes. ..
  58. Kirchgessner H, Dietrich J, Scherer J, Isomaki P, Korinek V, Hilgert I, et al. The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain. J Exp Med. 2001;193:1269-84 pubmed
  59. Hombach A, Wieczarkowiecz A, Marquardt T, Heuser C, Usai L, Pohl C, et al. Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol. 2001;167:6123-31 pubmed
  60. Reyes Gibby C, Wang J, Silvas M, Yu R, Yeung S, Shete S. MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients. BMC Genet. 2016;17:40 pubmed publisher
    ..88 × 10(-3); OR = 1.32, 95 % CI: 1.09-1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 × 10(-3); OR = 0.76, 95 % CI: 0.62-0.93)...
  61. Park Y, Jin L, Bennett K, Wang D, Fredenburg K, Tseng J, et al. CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma. Oral Oncol. 2018;78:145-150 pubmed publisher
    ..CD70-specific CAR-T cells specifically recognized and efficiently eliminated CD70-positive HNSCC cells. This study provides the basis for further investigation into CD70 and other CAR-T targets. ..
  62. Housden H, Skipp P, Crump M, Broadbridge R, Crabbe T, Perry M, et al. Investigation of the kinetics and order of tyrosine phosphorylation in the T-cell receptor zeta chain by the protein tyrosine kinase Lck. Eur J Biochem. 2003;270:2369-76 pubmed
  63. Lopez Santalla M, Krishnan S, Valeri A, Aguilera Montilla N, Fisher C, Perez Blas M, et al. Defective CD3zeta chain expression in Herpesvirus saimiri (HVS)-derived T-cell lines in gastric adenocarcinoma. Cell Immunol. 2005;238:113-22 pubmed
    Low expression of the CD3zeta chain has been reported in patients with cancer and it has been suggested that tumor-derived factors are involved in its downregulation...
  64. Fornari T, Donate P, Assis A, Macedo C, Sakamoto Hojo E, Donadi E, et al. Comprehensive Survey of miRNA-mRNA Interactions Reveals That Ccr7 and Cd247 (CD3 zeta) are Posttranscriptionally Controlled in Pancreas Infiltrating T Lymphocytes of Non-Obese Diabetic (NOD) Mice. PLoS ONE. 2015;10:e0142688 pubmed publisher
    ..The interactions between miR-202-3p and the Ccr7 chemokine receptor mRNA or Cd247 (Cd3 zeta chain) mRNA found in PILs are highlighted because these interactions can contribute to a better understanding of ..
  65. Bunnell S, Hong D, Kardon J, Yamazaki T, McGlade C, Barr V, et al. T cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol. 2002;158:1263-75 pubmed
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    ..We determined the prevalence of TCR zeta chain deficiency in SLE from a large cohort of unselected racially diverse patients with different levels of ..
  67. Palacios E, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene. 2004;23:7990-8000 pubmed
    ..SFKs are required for each of these TCR-based signals, and Lck seems to be the major contributor. ..
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    ..These data provide evidence for SLAP-dependent regulation of CD3 ?-chain in the fine control of TCR signaling. ..
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    ..This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes. ..
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    ..The in vivo association of SLAP with key signaling molecules and its inhibition of T cell activation suggests that SLAP plays an important role in TCR-mediated signal transduction. ..
  72. Liu T, Chen F, Tang N, Feng J, Zhao D, Wei K, et al. CD247 can bind SHC1, no matter if CD247 is phosphorylated. J Mol Recognit. 2009;22:205-14 pubmed publisher
    ..src homology 2 domain-containing transforming protein C1 (SHC1) had been found to bind the tyrosine-phosphorylated CD247 chain of the receptor via its src homology 2 (SH2) domain, delivering signals that control T cell development and ..
  73. Dieude P, Boileau C, Guedj M, Avouac J, Ruiz B, Hachulla E, et al. Independent replication establishes the CD247 gene as a genetic systemic sclerosis susceptibility factor. Ann Rheum Dis. 2011;70:1695-6 pubmed publisher
  74. Loviglio M, Arbogast T, Jønch A, Collins S, Popadin K, Bonnet C, et al. The Immune Signaling Adaptor LAT Contributes to the Neuroanatomical Phenotype of 16p11.2 BP2-BP3 CNVs. Am J Hum Genet. 2017;101:564-577 pubmed publisher
    ..hypothesis that LAT dosage is relevant to the CNV pathology, we observed similar effects upon overexpression of CD247 and ZAP70, encoding members of the LAT signalosome...
  75. Dang N, Torimoto Y, Shimamura K, Tanaka T, Daley J, Schlossman S, et al. 1F7 (CD26): a marker of thymic maturation involved in the differential regulation of the CD3 and CD2 pathways of human thymocyte activation. J Immunol. 1991;147:2825-32 pubmed
    ..anti-1F7 reactivity is found on medullary thymocytes, the population of thymocytes expressing high level of CD3 (CD3H)...
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    ..the cysteine residue at the catalytic center was changed to a serine residue, bound tightly to the phosphorylated CD3 zeta chain...
  78. Nel A, Gupta S, Lee L, Ledbetter J, Kanner S. Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR. J Biol Chem. 1995;270:18428-36 pubmed
    ..Taken together, these results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70 complexes, which localize in the vicinity of TCR-zeta. ..
  79. Boussiotis V, Barber D, Lee B, Gribben J, Freeman G, Nadler L. Differential association of protein tyrosine kinases with the T cell receptor is linked to the induction of anergy and its prevention by B7 family-mediated costimulation. J Exp Med. 1996;184:365-76 pubmed
  80. Raab M, da Silva A, Findell P, Rudd C. Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2. Immunity. 1997;6:155-64 pubmed
    ..10 induces IL-2 production without detectable Vav-SLP-76 binding. Therefore, despite effects of Vav-SLP-76 on IL-2 expression, Vav-SLP-76 binding per se is not essential for IL-2 production in all T cells. ..
  81. Arndt B, Krieger T, Kalinski T, Thielitz A, Reinhold D, Roessner A, et al. The transmembrane adaptor protein SIT inhibits TCR-mediated signaling. PLoS ONE. 2011;6:e23761 pubmed publisher
    ..In summary, the data identify SIT as an important modulator of TCR-mediated signaling that regulates T-cell activation, homeostasis and tolerance. ..
  82. Gudelj L, Deniz G, Rukavina D, Johnson P, Christmas S. Expression of functional molecules by human CD3- decidual granular leucocyte clones. Immunology. 1996;87:609-15 pubmed
    ..Both cytoplasmic CD3 zeta and CD3 epsilon chains were detected in > 90% of DGL clones in the absence of cell surface CD3...
  83. Tsuzaka K, Nozaki K, Kumazawa C, Shiraishi K, Setoyama Y, Yoshimoto K, et al. DNA microarray gene expression profile of T cells with the splice variants of TCRzeta mRNA observed in systemic lupus erythematosus. J Immunol. 2006;176:949-56 pubmed
    ..Identification of these responsive genes in T cells in which the zeta and TCR/CD3 complexes were down-regulated may help to better understand the pathogenesis of systemic lupus erythematosus. ..
  84. Zea A, Culotta K, Ali J, Mason C, Park H, Zabaleta J, et al. Decreased expression of CD3zeta and nuclear transcription factor kappa B in patients with pulmonary tuberculosis: potential mechanisms and reversibility with treatment. J Infect Dis. 2006;194:1385-93 pubmed
    ..The presence of arginase could, in part, explain the decreased expression of CD3zeta . These findings provide a novel mechanism that may explain the T cell dysfunction observed in patients with PTB. ..
  85. Mukherjee P, Kass I, Arkin I, Zanni M. Structural disorder of the CD3zeta transmembrane domain studied with 2D IR spectroscopy and molecular dynamics simulations. J Phys Chem B. 2006;110:24740-9 pubmed
    ..Taken together, the simulations and experiments reveal that infrared line shapes are sensitive probes of membrane protein structural and environmental heterogeneity. ..
  86. Ferjeni Z, Bouzid D, Fourati H, Stayoussef M, Abida O, Kammoun T, et al. Association of TCR/CD3, PTPN22, CD28 and ZAP70 gene polymorphisms with type 1 diabetes risk in Tunisian population: family based association study. Immunol Lett. 2015;163:1-7 pubmed publisher
    ..782; p=0.005) of TCRβ gene. We also demonstrated that rs10918706 in the intron of the CD3z gene was associated with increased risk of T1D (Z score 2.137; p=0.032). In the same region, rs2949655 (Z score=2...
  87. Martins M, Williams A, Comeau M, Marion M, Ziegler J, Freedman B, et al. Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study. Genes Immun. 2015;16:142-50 pubmed publisher
    ..However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts...
  88. Tauber S, Hauschild S, Paulsen K, Gutewort A, Raig C, Hürlimann E, et al. Signal transduction in primary human T lymphocytes in altered gravity during parabolic flight and clinostat experiments. Cell Physiol Biochem. 2015;35:1034-51 pubmed publisher
    ..We assume that a gravity condition around 1g is required for the expression of key surface receptors and appropriate regulation of signal molecules in T lymphocytes. ..
  89. Noraz N, Jaaoini I, Charoy C, Watrin C, Chounlamountri N, Benon A, et al. Syk kinases are required for spinal commissural axon repulsion at the midline via the ephrin/Eph pathway. Development. 2016;143:2183-93 pubmed publisher
    ..Moreover, we identified ephrin/Eph as guidance molecules utilizing the ITAM-bearing CD3zeta (Cd247) and associated Syk kinases for the growth cone collapse response induced in vitro Here, we show that in the ..
  90. Sturm R, Eyre H, Baker E, Sutherland G. The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23. Cytogenet Cell Genet. 1995;68:231-2 pubmed
    ..We report here the regional localization of OTF1 to 1q22-->q23 by fluorescence in situ hybridization. The physical linkage of the CD3Z gene to the OTF1 transcription unit also refines the location of the CD3Z locus to 1q22-->q23.
  91. Takeuchi T, Suzuki K. CD247 variants and single-nucleotide polymorphisms observed in systemic lupus erythematosus patients. Rheumatology (Oxford). 2013;52:1551-5 pubmed publisher
    SLE is associated with a deficiency in cluster of differentiation 247 (CD247, also known as CD3 zeta chain), a component of the T-cell receptor (TCR)-CD3 complex...