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NCR3  -  natural cytotoxicity triggering receptor 3

Homo sapiens

Synonyms: 1C7, Activating natural killer receptor p30, CD337, LY117, MALS, ...
 
 
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Disease relevance of NCR3

 

High impact information on NCR3

 

Chemical compound and disease context of NCR3

  • We have tested the effects of two Eli-Lilly compounds, LY 117, 018 and raloxifene, on E2-regulated and IGF-I-induced proliferation or AP-1 activity in human breast cancer cells [10].
 

Biological context of NCR3

 

Anatomical context of NCR3

  • The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk [1].
  • The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium [1].
  • Although mAb-mediated cross-linking of NKp30 induces strong NK cell activation, mAb-mediated masking inhibits the NK cytotoxicity against normal or tumor target cells [14].
  • A number of alternatively spliced transcripts of 1C7 were identified by reverse transcriptase-PCR, all of which are expressed in immune-related cell lines [15].
  • More than 95% of peripheral blood and 85% of spleen NK cells are CD56(dim)CD16(+) and express perforin, the natural cytotoxicity receptors (NCRs) NKp30 and NKp46, as well as in part killer cell Ig-like receptors (KIRs) [16].
 

Associations of NCR3 with chemical compounds

  • NKp30 has been mapped to the HLA class III region near tumor necrosis factor (TNF) family loci [17].
  • Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan [4].
  • We demonstrate that target cell surface heparan sulfate proteoglycans (HSPGs) are recognized by NKp30 and NKp46 and that 6-O-sulfation and N-acetylation state of the glucose building unit affect this recognition and lysis by NK cells [18].
  • In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced [19].
 

Regulatory relationships of NCR3

 

Other interactions of NCR3

  • LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and microbial infection [1].
  • NKG2D, together with NKp46 and NKp30, represents a major triggering receptor involved in the induction of cytotoxicity by both resting and activated human natural killer cells [23].
  • The activating NK receptors NKp30, NKG2D, and DNAM-1 represented the major receptors responsible for the induction of NK-mediated cytotoxicity against MSCs [24].
  • Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN [25].
  • NK cells generated after SCT exhibited an immature phenotype: the cytotoxic CD3- CD56(dim) subset was small, expression of KIRs and NKp30 was reduced, while CD94/NKG2A expression was increased [26].
 

Analytical, diagnostic and therapeutic context of NCR3

  • Molecular cloning of NKp30 cDNA revealed a member of the immunoglobulin superfamily, characterized by a single V-type domain and a charged residue in the transmembrane portion [14].
  • In addition, we have shown by reverse transcription-polymerase chain reaction (RT-PCR) analysis that the human NKp30 gene presents differential expression patterns in tissues [11].
  • Finally, the analysis of perforin-deficient NK cells allowed the dissection of the 2 NKp30-mediated NK-cell functions, since NKp30 could induce cytokine-dependent DC maturation in the absence of NK-mediated DC killing [27].
  • NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46 [28].
  • Method of study Peripheral blood NK cells (CD56(dim) and CD56(bright) were analyzed for the expression of NCRs (NKp46, NKp44 and NKp30) and a2V-ATPase using 3-color flow cytometry in women with RSA (n=24), implantation failures (n=19) or normal healthy women (n=13) [29].

References

  1. LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and microbial infection. Mulcahy, H., O'Rourke, K.P., Adams, C., Molloy, M.G., O'Gara, F. Immunogenetics (2006) [Pubmed]
  2. Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis C. Nattermann, J., Feldmann, G., Ahlenstiel, G., Langhans, B., Sauerbruch, T., Spengler, U. Gut (2006) [Pubmed]
  3. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Castriconi, R., Dondero, A., Corrias, M.V., Lanino, E., Pende, D., Moretta, L., Bottino, C., Moretta, A. Cancer Res. (2004) [Pubmed]
  4. Evidence that the cellular ligand for the human NK cell activation receptor NKp30 is not a heparan sulfate glycosaminoglycan. Warren, H.S., Jones, A.L., Freeman, C., Bettadapura, J., Parish, C.R. J. Immunol. (2005) [Pubmed]
  5. Recognition of vaccinia virus-infected cells by human natural killer cells depends on natural cytotoxicity receptors. Chisholm, S.E., Reyburn, H.T. J. Virol. (2006) [Pubmed]
  6. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Moretta, A., Bottino, C., Vitale, M., Pende, D., Cantoni, C., Mingari, M.C., Biassoni, R., Moretta, L. Annu. Rev. Immunol. (2001) [Pubmed]
  7. Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Arnon, T.I., Achdout, H., Levi, O., Markel, G., Saleh, N., Katz, G., Gazit, R., Gonen-Gross, T., Hanna, J., Nahari, E., Porgador, A., Honigman, A., Plachter, B., Mevorach, D., Wolf, D.G., Mandelboim, O. Nat. Immunol. (2005) [Pubmed]
  8. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. Ferlazzo, G., Tsang, M.L., Moretta, L., Melioli, G., Steinman, R.M., Münz, C. J. Exp. Med. (2002) [Pubmed]
  9. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Castriconi, R., Cantoni, C., Della Chiesa, M., Vitale, M., Marcenaro, E., Conte, R., Biassoni, R., Bottino, C., Moretta, L., Moretta, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Anti-growth factor activities of benzothiophenes in human breast cancer cells. Freiss, G., Galtier, F., Puech, C., Aknin, C., Maudelonde, T., Chalbos, D., Vignon, F. J. Steroid Biochem. Mol. Biol. (2005) [Pubmed]
  11. NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an expressed gene in Mus caroli. Hollyoake, M., Campbell, R.D., Aguado, B. Mol. Biol. Evol. (2005) [Pubmed]
  12. NKp30-dependent cytolysis of filovirus-infected human dendritic cells. Fuller, C.L., Ruthel, G., Warfield, K.L., Swenson, D.L., Bosio, C.M., Aman, M.J., Bavari, S. Cell. Microbiol. (2007) [Pubmed]
  13. Deficient expression of NCR in NK cells from acute myeloid leukemia: evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Fauriat, C., Just-Landi, S., Mallet, F., Arnoulet, C., Sainty, D., Olive, D., Costello, R.T. Blood (2007) [Pubmed]
  14. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. Pende, D., Parolini, S., Pessino, A., Sivori, S., Augugliaro, R., Morelli, L., Marcenaro, E., Accame, L., Malaspina, A., Biassoni, R., Bottino, C., Moretta, L., Moretta, A. J. Exp. Med. (1999) [Pubmed]
  15. A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. Neville, M.J., Campbell, R.D. J. Immunol. (1999) [Pubmed]
  16. The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. Ferlazzo, G., Thomas, D., Lin, S.L., Goodman, K., Morandi, B., Muller, W.A., Moretta, A., Münz, C. J. Immunol. (2004) [Pubmed]
  17. Identification of novel single nucleotide substitutions in the NKp30 gene expressed in human natural killer cells. Sato, M., Ohashi, J., Tsuchiya, N., Tadokoro, K., Juji, T., Hanaoka, K., Tokunaga, K., Yabe, T. Tissue Antigens (2001) [Pubmed]
  18. Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. Bloushtain, N., Qimron, U., Bar-Ilan, A., Hershkovitz, O., Gazit, R., Fima, E., Korc, M., Vlodavsky, I., Bovin, N.V., Porgador, A. J. Immunol. (2004) [Pubmed]
  19. The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicity. Vitale, C., Chiossone, L., Cantoni, C., Morreale, G., Cottalasso, F., Moretti, S., Pistorio, A., Haupt, R., Lanino, E., Dini, G., Moretta, L., Mingari, M.C. Eur. J. Immunol. (2004) [Pubmed]
  20. Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes. Zambello, R., Falco, M., Della Chiesa, M., Trentin, L., Carollo, D., Castriconi, R., Cannas, G., Carlomagno, S., Cabrelle, A., Lamy, T., Agostini, C., Moretta, A., Semenzato, G., Vitale, M. Blood (2003) [Pubmed]
  21. The maturation potential of NK cell clones toward autologous dendritic cells correlates with HMGB1 secretion. Semino, C., Ceccarelli, J., Lotti, L.V., Torrisi, M.R., Angelini, G., Rubartelli, A. J. Leukoc. Biol. (2007) [Pubmed]
  22. Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Pogge von Strandmann, E., Simhadri, V.R., von Tresckow, B., Sasse, S., Reiners, K.S., Hansen, H.P., Rothe, A., Böll, B., Simhadri, V.L., Borchmann, P., McKinnon, P.J., Hallek, M., Engert, A. Immunity (2007) [Pubmed]
  23. Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Pende, D., Rivera, P., Marcenaro, S., Chang, C.C., Biassoni, R., Conte, R., Kubin, M., Cosman, D., Ferrone, S., Moretta, L., Moretta, A. Cancer Res. (2002) [Pubmed]
  24. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Spaggiari, G.M., Capobianco, A., Becchetti, S., Mingari, M.C., Moretta, L. Blood (2006) [Pubmed]
  25. Association of HLA-A*3303-B*4403-DRB1*1302 haplotype, but not of TNFA promoter and NKp30 polymorphism, with postherpetic neuralgia (PHN) in the Japanese population. Sato, M., Ohashi, J., Tsuchiya, N., Kashiwase, K., Ishikawa, Y., Arita, H., Hanaoka, K., Tokunaga, K., Yabe, T. Genes Immun. (2002) [Pubmed]
  26. NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Nguyen, S., Dhedin, N., Vernant, J.P., Kuentz, M., Al Jijakli, A., Rouas-Freiss, N., Carosella, E.D., Boudifa, A., Debré, P., Vieillard, V. Blood (2005) [Pubmed]
  27. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Vitale, M., Della Chiesa, M., Carlomagno, S., Pende, D., Aricò, M., Moretta, L., Moretta, A. Blood (2005) [Pubmed]
  28. NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. Spaggiari, G.M., Carosio, R., Pende, D., Marcenaro, S., Rivera, P., Zocchi, M.R., Moretta, L., Poggi, A. Eur. J. Immunol. (2001) [Pubmed]
  29. Expression of Natural Cytotoxicity Receptors and a2V-ATPase on Peripheral Blood NK Cell Subsets in Women with Recurrent Spontaneous Abortions and Implantation Failures. Fukui, A., Ntrivalas, E., Gilman-Sachs, A., Kwak-Kim, J., Lee, S.K., Levine, R., Beaman, K. Am. J. Reprod. Immunol. (2006) [Pubmed]
 
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