Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 23 February 2010
Vol. 3, Issue 110, p. ra14
[DOI: 10.1126/scisignal.2000467]

RESEARCH ARTICLES

DNA-PKcs Controls an Endosomal Signaling Pathway for a Proinflammatory Response by Natural Killer Cells

Sumati Rajagopalan1*, Mark W. Moyle1, Irma Joosten2, and Eric O. Long1*

1 Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
2 Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, the Netherlands.

Abstract: Endosomes are emerging as specialized signaling compartments that endow receptors with distinct signaling properties. The diversity of endosomal signaling pathways and their contribution to various biological responses is still unclear. CD158d, which is also known as the killer cell immunoglobulin-like receptor (KIR) 2DL4 (KIR2DL4), is an endosome-resident receptor in natural killer (NK) cells that stimulates the release of a unique set of proinflammatory and proangiogenic mediators in response to soluble human leukocyte antigen G (HLA-G). Here, we identified the CD158d signaling cascade. In response to soluble agonist antibody or soluble HLA-G, signaling by CD158d was dependent on the activation of nuclear factor {kappa}B (NF-{kappa}B) and the serine-threonine kinase Akt. CD158d associated with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), promoted the recruitment of Akt to endosomes, and stimulated the DNA-PKcs–dependent phosphorylation of Akt. The sequential requirement for DNA-PKcs, Akt, and NF-{kappa}B in signaling by CD158d delineates a previously uncharacterized endosomal signaling pathway for a proinflammatory response in NK cells.

* To whom correspondence should be addressed. E-mail: sumi{at}nih.gov (S.R.) and eLong{at}nih.gov (E.O.L.)

Citation: S. Rajagopalan, M. W. Moyle, I. Joosten, E. O. Long, DNA-PKcs Controls an Endosomal Signaling Pathway for a Proinflammatory Response by Natural Killer Cells. Sci. Signal. 3, ra14 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inositol tetrakisphosphate limits NK cell effector functions by controlling PI3K signaling.
K. Sauer, E. Park, S. Siegemund, A. R. French, J. A. Wahle, L. Sternberg, S. Rigaud, A. H. Jonsson, W. M. Yokoyama, and Y. H. Huang (2013)
Blood 121, 286-297
   Abstract »    Full Text »    PDF »
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
S. Rajagopalan and E. O. Long (2012)
PNAS 109, 20596-20601
   Abstract »    Full Text »    PDF »
Natural killer cell-produced IFN-{gamma} and TNF-{alpha} induce target cell cytolysis through up-regulation of ICAM-1.
R. Wang, J. J. Jaw, N. C. Stutzman, Z. Zou, and P. D. Sun (2012)
J. Leukoc. Biol. 91, 299-309
   Abstract »    Full Text »    PDF »
Ubiquitylation of an Internalized Killer Cell Ig-Like Receptor by Triad3A Disrupts Sustained NF-{kappa}B Signaling.
S. M. S. Miah, A. K. Purdy, N. B. Rodin, A. W. MacFarlane IV, J. Oshinsky, D. A. Alvarez-Arias, and K. S. Campbell (2011)
J. Immunol. 186, 2959-2969
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882