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Ly6a  -  lymphocyte antigen 6 complex, locus A

Mus musculus

 
 
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Disease relevance of Ly6a

 

Psychiatry related information on Ly6a

 

High impact information on Ly6a

  • Despite many efforts, the nature of thymic immigrants that give rise to T cells has remained obscure, especially since it became known that extrathymic lineage-negative, Sca-1-positive, c-kit high progenitor cells differ from intrathymic early T cell progenitors (ETPs) by functional potential and dependence on Notch signaling [7].
  • Five mAbs have been generated and used to characterize TAP (T cell activating protein) a novel, functional murine T cell membrane antigen [8].
  • Moreover, this culture system yielded side population and Sca-1-positive cell populations that included hepatic stem/progenitor cells with differentiation and proliferation properties [9].
  • Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family [10].
  • To isolate a Ly-6 cDNA, synthetic oligonucleotides, based on the partial amino acid sequence of purified Ly-6E.1 protein, were used to probe a cDNA library [11].
 

Biological context of Ly6a

  • To address the question whether LY6A has a function in spermatogenesis or testis development, we studied the testis of Ly6a(-/-) mice (allele Ly6a(tm1Pmf)) [12].
  • We identified several overlapping P1 artificial chromosomes containing the Sca-1 gene and mapped one of these to mouse chromosome 15D3.1-3.3, the region previously shown to contain members of the murine Ly-6 gene family [13].
  • To characterize the control elements of this gene, we have cloned a 30-kb fragment encoding a fully functional Ly-6E.1 gene and 13 kb of 5' and 13 kb of 3' flanking sequence [1].
  • The Sca-1 antibody recognizes antigens encoded by members of the Ly-6 multigene family [1].
  • Ly-6E.1 is highly expressed in murine tumor cells with a high malignancy phenotype and may serve as a marker for such a phenotype [14].
 

Anatomical context of Ly6a

 

Associations of Ly6a with chemical compounds

  • In addition, Sca-1(-/-) mice were injected with 5-FU and Lin(-) cells were analyzed [15].
  • Sca-1(+) mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1'-dioctadecyl- 3,3,3,'3'-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium [17].
  • The expression of Sca-1 was enhanced on the surface of LSEC by tumor necrosis factor (TNF) [16].
  • We have characterized the TAP molecule, an Ly-6 linked T-cell-activating glycoprotein [18].
  • To further examine whether Ly-6A.2 mediates adhesion (versus inducing another adhesion pathway) reaggregation assays were performed with paraformaldehyde-fixed Tg+ thymocytes [19].
 

Regulatory relationships of Ly6a

 

Other interactions of Ly6a

  • Characterization of Ly-6M, a novel member of the Ly-6 family of hematopoietic proteins [13].
  • Electrophoretic analysis showed a similar size and charge for Ly-6A.2, Ly-6B.2, Ly-6D.2, and Ly-27 [25].
  • In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies [26].
  • Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family [27].
  • The primary structure of the newly identified HDL-binding protein resembles GPI-anchored proteins consisting of an N-terminal signal sequence, an acidic region with a cluster of aspartate and glutamate residues, an Ly-6 motif highly conserved among the lymphocyte antigen family, and a C-terminal hydrophobic region [28].
 

Analytical, diagnostic and therapeutic context of Ly6a

  • 1. On western blots of lymphocyte surface proteins which had been solubilized and electrophoretically separated in octylglucoside, they detected bands which comigrated with Ly-6A.2 or Ly-6E.1 antigens [25].
  • Immunocytochemistry was performed to identify the bone marrow origin of the cells in the RPE using antibodies for CD45, Sca-1, and c-kit, as well as the expression of the RPE-specific marker, RPE-65 [29].
  • On cells or in an immunoassay they blocked alloantibodies against Ly-6A.2 or Ly-6E [25].
  • The expression of Sca-1 in LSEC was confirmed at the mRNA and protein level by reverse transcriptase (RT)-PCR, flow cytometry, and immunofluorescence studies [16].
  • We examined whether Sca-1 ligation on the surface of LSEC regulates some biological response in these cells [16].

References

  1. Cloning of the complete Ly-6E.1 gene and identification of DNase I hypersensitive sites corresponding to expression in hematopoietic cells. Sinclair, A.M., Dzierzak, E.A. Blood (1993) [Pubmed]
  2. The differentiation antigen Ly-6E.1 is expressed in mouse metastatic tumor cell lines. Cohn, M.A., Kramerov, D., Hulgaard, E.F., Lukanidin, E.M. FEBS Lett. (1997) [Pubmed]
  3. Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point. Rothenberg, E.V., Chen, D., Diamond, R.A. J. Immunol. (1993) [Pubmed]
  4. E mu-bcl-2 transgene facilitates spontaneous transformation of early pre-B and immunoglobulin-secreting cells but not T cells. Strasser, A., Harris, A.W., Cory, S. Oncogene (1993) [Pubmed]
  5. Dual roles of telomerase in cardiac protection and repair. Schneider, M.D. Novartis Found. Symp. (2006) [Pubmed]
  6. Gene gun-mediated IL-12 gene therapy induces antitumor effects in the absence of toxicity: a direct comparison with systemic IL-12 protein therapy. Rakhmilevich, A.L., Timmins, J.G., Janssen, K., Pohlmann, E.L., Sheehy, M.J., Yang, N.S. J. Immunother. (1999) [Pubmed]
  7. Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands. Krueger, A., Garbe, A.I., von Boehmer, H. J. Exp. Med. (2006) [Pubmed]
  8. TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes. Rock, K.L., Yeh, E.T., Gramm, C.F., Haber, S.I., Reiser, H., Benacerraf, B. J. Exp. Med. (1986) [Pubmed]
  9. Long-term extensive expansion of mouse hepatic stem/progenitor cells in a novel serum-free culture system. Tsuchiya, A., Heike, T., Fujino, H., Shiota, M., Umeda, K., Yoshimoto, M., Matsuda, Y., Ichida, T., Aoyagi, Y., Nakahata, T. Gastroenterology (2005) [Pubmed]
  10. The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion. Brakenhoff, R.H., Gerretsen, M., Knippels, E.M., van Dijk, M., van Essen, H., Weghuis, D.O., Sinke, R.J., Snow, G.B., van Dongen, G.A. J. Cell Biol. (1995) [Pubmed]
  11. Isolation of a murine Ly-6 cDNA reveals a new multigene family. LeClair, K.P., Palfree, R.G., Flood, P.M., Hammerling, U., Bothwell, A. EMBO J. (1986) [Pubmed]
  12. LY6A/E (SCA-1) expression in the mouse testis. van Bragt, M.P., Ciliberti, N., Stanford, W.L., de Rooij, D.G., van Pelt, A.M. Biol. Reprod. (2005) [Pubmed]
  13. Characterization of Ly-6M, a novel member of the Ly-6 family of hematopoietic proteins. Patterson, J.M., Johnson, M.H., Zimonjic, D.B., Graubert, T.A. Blood (2000) [Pubmed]
  14. Expression of Ly-6, a marker for highly malignant murine tumor cells, is regulated by growth conditions and stress. Treister, A., Sagi-Assif, O., Meer, M., Smorodinsky, N.I., Anavi, R., Golan, I., Meshel, T., Kahana, O., Eshel, R., Katz, B.Z., Shevach, E., Witz, I.P. Int. J. Cancer (1998) [Pubmed]
  15. Roles of Sca-1 in hematopoietic stem/progenitor cell function. Bradfute, S.B., Graubert, T.A., Goodell, M.A. Exp. Hematol. (2005) [Pubmed]
  16. Expression of the hematopoietic stem cell antigen Sca-1 (LY-6A/E) in liver sinusoidal endothelial cells: possible function of Sca-1 in endothelial cells. Luna, G., Paez, J., Cardier, J.E. Stem cells and development. (2004) [Pubmed]
  17. A systemic provascular response in bone marrow to musculoskeletal trauma in mice. Laing, A.J., Dillon, J.P., Condon, E.T., Coffey, J.C., Street, J.T., Wang, J.H., McGuinness, A.J., Redmond, H.P. The Journal of bone and joint surgery. British volume (2007) [Pubmed]
  18. Biosynthesis, glycosylation, and partial N-terminal amino acid sequence of the T-cell-activating protein TAP. Reiser, H., Coligan, J., Benacerraf, B., Rock, K.L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  19. Overexpressed Ly-6A.2 mediates cell-cell adhesion by binding a ligand expressed on lymphoid cells. Bamezai, A., Rock, K.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  20. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. Matsuura, K., Nagai, T., Nishigaki, N., Oyama, T., Nishi, J., Wada, H., Sano, M., Toko, H., Akazawa, H., Sato, T., Nakaya, H., Kasanuki, H., Komuro, I. J. Biol. Chem. (2004) [Pubmed]
  21. TNFalpha and anti-Fas antibodies regulate Ly-6E.1 expression by tumor cells: a possible link between angiogenesis and Ly-6E.1. Sagi-Assif, O., Traister, A., Katz, B.Z., Anavi, R., Eskenasy, M., Witz, I.P. Immunol. Lett. (1996) [Pubmed]
  22. Ly-6A.2 expression regulates antigen-specific CD4+ T cell proliferation and cytokine production. Henderson, S.C., Kamdar, M.M., Bamezai, A. J. Immunol. (2002) [Pubmed]
  23. The T-cell activating protein (TAP) is up-regulated by endogenous IFN-gamma in activated T cells. Dumont, F.J., Palfree, R.G., Fisher, P.A. Immunology (1988) [Pubmed]
  24. Selective up-regulation by interferon-gamma of surface molecules of the Ly-6 complex in resting T cells: the Ly-6A/E and TAP antigens are preferentially enhanced. Dumont, F.J., Dijkmans, R., Palfree, R.G., Boltz, R.D., Coker, L. Eur. J. Immunol. (1987) [Pubmed]
  25. Ly-6A.2 and Ly-6E.1 molecules are antithetical and identical to MALA-1. Palfree, R.G., Dumont, F.J., Hammerling, U. Immunogenetics (1986) [Pubmed]
  26. Isolation and characterization of cDNA clones for the mouse thymocyte B cell antigen (ThB). Gumley, T.P., McKenzie, I.F., Kozak, C.A., Sandrin, M.S. J. Immunol. (1992) [Pubmed]
  27. Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family. van de Rijn, M., Heimfeld, S., Spangrude, G.J., Weissman, I.L. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  28. Expression cloning and characterization of a novel glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein, GPI-HBP1. Ioka, R.X., Kang, M.J., Kamiyama, S., Kim, D.H., Magoori, K., Kamataki, A., Ito, Y., Takei, Y.A., Sasaki, M., Suzuki, T., Sasano, H., Takahashi, S., Sakai, J., Fujino, T., Yamamoto, T.T. J. Biol. Chem. (2003) [Pubmed]
  29. 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]
 
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