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Science 30 July 1999:
Vol. 285. no. 5428, pp. 730 - 732
DOI: 10.1126/science.285.5428.730
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Reports

An Activating Immunoreceptor Complex Formed by NKG2D and DAP10

Jun Wu, 1 Yaoli Song, 1 Alexander B. H. Bakker, 1 Stefan Bauer, 2 Thomas Spies, 2 Lewis L. Lanier, 1* Joseph H. Phillips 1

Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.

1 DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.
2 Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA.
*   To whom correspondence should be addressed. E-mail: lanier{at}dnax.org

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NF-{kappa}B Regulates Expression of the MHC Class I-Related Chain A Gene in Activated T Lymphocytes.
L. L. Molinero, M. B. Fuertes, M. V. Girart, L. Fainboim, G. A. Rabinovich, M. A. Costas, and N. W. Zwirner (2004)
J. Immunol. 173, 5583-5590
   Abstract »    Full Text »    PDF »
Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis.
A. Ahmad and F. Alvarez (2004)
J. Leukoc. Biol. 76, 743-759
   Abstract »    Full Text »    PDF »
Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity.
M. Cella, K. Fujikawa, I. Tassi, S. Kim, K. Latinis, S. Nishi, W. Yokoyama, M. Colonna, and W. Swat (2004)
J. Exp. Med. 200, 817-823
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Signal Regulatory Protein {alpha}1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling.
G. S. Kapoor, D. Kapitonov, and D. M. O'Rourke (2004)
Cancer Res. 64, 6444-6452
   Abstract »    Full Text »    PDF »
Cross-Talk between Activated Human NK Cells and CD4+ T Cells via OX40-OX40 Ligand Interactions.
A. Zingoni, T. Sornasse, B. G. Cocks, Y. Tanaka, A. Santoni, and L. L. Lanier (2004)
J. Immunol. 173, 3716-3724
   Abstract »    Full Text »    PDF »
A Structural Basis for the Association of DAP12 with Mouse, but Not Human, NKG2D.
D. B. Rosen, M. Araki, J. A. Hamerman, T. Chen, T. Yamamura, and L. L. Lanier (2004)
J. Immunol. 173, 2470-2478
   Abstract »    Full Text »    PDF »
Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages.
J. Siren, T. Sareneva, J. Pirhonen, M. Strengell, V. Veckman, I. Julkunen, and S. Matikainen (2004)
J. Gen. Virol. 85, 2357-2364
   Abstract »    Full Text »    PDF »
Involvement of FcR{gamma} in signal transduction of osteoclast-associated receptor (OSCAR).
S. Ishikawa, N. Arase, T. Suenaga, Y. Saita, M. Noda, T. Kuriyama, H. Arase, and T. Saito (2004)
Int. Immunol. 16, 1019-1025
   Abstract »    Full Text »    PDF »
Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells.
T. Igarashi, J. Wynberg, R. Srinivasan, B. Becknell, J. P. McCoy Jr, Y. Takahashi, D. A. Suffredini, W. M. Linehan, M. A. Caligiuri, and R. W. Childs (2004)
Blood 104, 170-177
   Abstract »    Full Text »    PDF »
Mechanisms of V{delta}1 {gamma}{delta} T Cell Activation by Microbial Components.
H. Das, M. Sugita, and M. B. Brenner (2004)
J. Immunol. 172, 6578-6586
   Abstract »    Full Text »    PDF »
Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes.
P. K. Epling-Burnette, J. S. Painter, P. Chaurasia, F. Bai, S. Wei, J. Y. Djeu, and T. P. Loughran Jr (2004)
Blood 103, 3431-3439
   Abstract »    Full Text »    PDF »
Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells.
M. R. Verneris, M. Karami, J. Baker, A. Jayaswal, and R. S. Negrin (2004)
Blood 103, 3065-3072
   Abstract »    Full Text »    PDF »
Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D.
K. Eleme, S. B. Taner, B. Onfelt, L. M. Collinson, F. E. McCann, N. J. Chalupny, D. Cosman, C. Hopkins, A. I. Magee, and D. M. Davis (2004)
J. Exp. Med. 199, 1005-1010
   Abstract »    Full Text »    PDF »
Architectural Changes in the TCR:CD3 Complex Induced by MHC:Peptide Ligation.
N. L. La Gruta, H. Liu, S. Dilioglou, M. Rhodes, D. L. Wiest, and D. A. A. Vignali (2004)
J. Immunol. 172, 3662-3669
   Abstract »    Full Text »    PDF »


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