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 journalArticle

229 Citations (Scopus)

Abstract

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
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2003

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Immunoreceptor Tyrosine-Based Activation Motif
NK Cell Lectin-Like Receptor Subfamily K
Natural Killer Cells
Tail
Phosphatidylinositol 3-Kinase
rho GTP-Binding Proteins
Amino Acid Motifs
Type C Phospholipases
Lymphocyte Activation
Protein-Tyrosine Kinases
Ligands
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. / Billadeau, Daniel D; Upshaw, Jadee L.; Schoon, Renee A.; Dick, Christopher J.; Leibson, Paul J.

In: Nature Immunology, Vol. 4, No. 6, 01.06.2003, p. 557-564.

Research output: Contribution to journalArticle

Billadeau, Daniel D ; Upshaw, Jadee L. ; Schoon, Renee A. ; Dick, Christopher J. ; Leibson, Paul J. / NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. In: Nature Immunology. 2003 ; Vol. 4, No. 6. pp. 557-564.
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