Research ArticleImmunology

Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells

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Science Signaling  27 Oct 2015:
Vol. 8, Issue 400, pp. ra108
DOI: 10.1126/scisignal.aab2724

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Turning on natural killer cells

Ligands present on the surface of tumor cells stimulate and activate natural killer (NK) cells of the innate immune system, which then trigger tumor cell death. Quatrini et al. found that the ligand-dependent internalization of a complex containing the stimulatory receptor NKG2D and the adaptor protein DAP10 depended on DAP10 ubiquitylation. Internalized receptor complexes in endosomes stimulated signaling by the kinase ERK, which was required for the secretion of cytolytic granules. Mutation of DAP10 to prevent its ubiquitylation resulted in decreased receptor internalization and defective cytotoxic responses, indicating that internalized receptors stimulate NK cell functions.