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


Editor's Summary

Under the Surface
In addition to serving as compartments in which signaling by internalized receptors is terminated, endosomes provide venues in which other receptors continue to signal or even trigger alternative pathways. Indeed, some receptors that fail to signal at the membrane function efficiently in endosomes. CD158d, an endosome-resident, immunoglobulin-like receptor found mostly in natural killer (NK) cells, triggers a proinflammatory and proangiogenic pathway in response to soluble human leukocyte antigen G (HLA-G). Uptake of fetal trophoblast–derived HLA-G by maternal NK cells may trigger the vascular remodeling required to establish an effective blood supply to the fetus, but how CD158d stimulates this response is unclear. Rajagopalan et al. found that endosomal CD158d activated nuclear factor {kappa}B (NF-{kappa}B) through a mechanism that depended on the kinase Akt, but not phosphatidylinositol 3-kinase (PI3K). In addition, CD158d associated with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which phosphorylated Akt at the endosome. In addition to expanding the known roles of DNA-PKcs, this study also highlights a PI3K-independent, endosomal function for Akt that is required for a proinflammatory response in NK cells.

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).

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Comment on "Killer Ig-like Receptor 2DL4 Does Not Mediate NK Cell IFN-{gamma} Responses to Soluble HLA-G Preparations".
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J. Immunol. 192, 714-721
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T. J. Mulrooney, P. E. Posch, and C. K. Hurley (2013)
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Blood 121, 286-297
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Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
S. Rajagopalan and E. O. Long (2012)
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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
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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
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