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

Published

Journal Article

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-Ile-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.

Full Text

Duke Authors

Cited Authors

  • Billadeau, DD; Upshaw, JL; Schoon, RA; Dick, CJ; Leibson, PJ

Published Date

  • June 2003

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 557 - 564

PubMed ID

  • 12740575

Pubmed Central ID

  • 12740575

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni929

Language

  • eng

Conference Location

  • United States