NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway

Daniel D. Billadeau, Jadee L. Upshaw, Renee A. Schoon, Christopher J. Dick, Paul J. Leibson

Research output: Contribution to journalArticlepeer-review

244 Scopus citations


The immune recognition receptor complex NKG2D-DAP10 on natural killer cells is stimulated by specific ligands carried on virus-infected and malignant cells. Because DAP10 does not have an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic tail, its ability to trigger killing has been debated. Here we show that a crucial Tyr-lle-Asn-Met amino acid motif in the cytoplasmic tail of DAP10 couples receptor stimulation to the downstream activation of phosphatidylinositol 3-kinase, Vav1, Rho family GTPases and phospholipase C. Unlike that of ITAM-containing receptors, the activation of NKG2D-DAP10 proceeds independently of Syk family protein tyrosine kinases. Yet the signals initiated by NKG2D-DAP10 are fully capable of inducing killing. Our findings identify a previously unknown mechanism by which receptor complexes that lack ITAM motifs can trigger lymphocyte activation.

Original languageEnglish (US)
Pages (from-to)557-564
Number of pages8
JournalNature immunology
Issue number6
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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