Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Versatile signaling through NKG2D

Nature Immunology volume 3, pages 1119–1120 (2002)Cite this article

Receptors in the immune system usually specialize in transmitting specific types of signals. However, by associating with two different signaling subunits, the receptor NKG2D can transmit distinct signals for either costimulation or full-fledged activation.

The signaling capability of many receptors in the immune system is controlled by their association with partner chains that carry specific sequence motifs for the recruitment of signaling molecules. Some of the activating receptors associate with subunits that carry immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tail. These include subunits of the T cell receptor (TCR)-associated CD3 complex, immunoglobulin α (Igα) and Igβ subunits of the B cell receptor, the γ chain of Fc receptors and of several natural killer (NK) cell receptors and DAP12, which associates with several receptors on NK cells and myeloid cells. Tyrosine-phosphorylated ITAMs deliver activation signals by recruiting the tyrosine kinases Syk or ZAP-70. A different tyrosine motif (YxxM) is found on receptors that provide costimulation, such as CD28 in T cells and the DAP10 partner chain of the receptor NKG2D1. Tyrosine-phosphorylated DAP10 may signal for costimulation by binding to the p85 subunit of phosphatidylinositol-3 kinase and to Grb21,2. The delivery of primary and accessory signals from receptors on immune cells must be carefully balanced not only to initiate cellular responses but also to control them by fine-tuning the extent of activation, cell death or inhibition. It came as a surprise, therefore, when Raulet and colleagues3 and Colonna and colleagues4 in this issue of Nature Immunology showed that the receptor NKG2D can provide both types of signals: costimulation through YxxM-containing DAP10 and activation through ITAM-containing DAP12.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Versatile signaling by the NKG2D receptor.

K. R.

References

  1. Wu, J. et al. Science 285, 730–732 (1999).

    Article  CAS  Google Scholar 

  2. Chang, C. et al. J. Immunol. 163, 4651–4654 (1999).

    CAS  PubMed  Google Scholar 

  3. Diefenbach, A. et al. Nature Immunol. 3, 1142–1149 (2002).

    Article  CAS  Google Scholar 

  4. Gilfillan, S., Ho, E.L., Cella, M., Yokoyama, W.M. & Colonna, M. Nature Immunol. 3, 1150–1155 (2002).

    Article  CAS  Google Scholar 

  5. Groh, V. et al. Nature Immunol. 2, 255–260 (2001).

    Article  CAS  Google Scholar 

  6. Cerwenka, A. & Lanier, L.L. Nature Rev. Immunol. 1, 41–49 (2001).

    Article  CAS  Google Scholar 

  7. Jamieson, A.M. et al. Immunity 17, 19–29 (2002).

    Article  CAS  Google Scholar 

  8. Carayannopoulos, L.N., Naidenko, O.V., Fremont, D.H. & Yokoyama, W.M. J. Immunol. 169, 4079–4083 (2002).

    Article  CAS  Google Scholar 

  9. Wu, J., Cherwinski, H., Spies, T., Phillips, J.H. & Lanier, L.L. J. Exp. Med. 192, 1059–1067 (2000).

    Article  CAS  Google Scholar 

  10. Lanier, L.L. & Bakker, A.B. Immunol. Today 21, 611–614 (2000).

    Article  CAS  Google Scholar 

  11. Sutherland, C.L., Chalupny, N.J., Schooley, K., VandenBos, T. & Cosman, D. J. Immunol. 168, 671–679 (2002).

    Article  CAS  Google Scholar 

  12. Namekawa, T. et al. J. Immunol. 165, 1138–1145 (2000).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, 20852, MD, USA

    Eric O. Long

Authors
  1. Eric O. Long
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Long, E. Versatile signaling through NKG2D. Nat Immunol 3, 1119–1120 (2002). https://doi.org/10.1038/ni1202-1119

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1202-1119

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing