NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway.
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.
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- src Homology Domains
- rho GTP-Binding Proteins
- Type C Phospholipases
- Syk Kinase
- Signal Transduction
- Receptors, Natural Killer Cell
- Receptors, Immunologic
- Proto-Oncogene Proteins c-vav
- Proto-Oncogene Proteins
- Protein-Tyrosine Kinases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- src Homology Domains
- rho GTP-Binding Proteins
- Type C Phospholipases
- Syk Kinase
- Signal Transduction
- Receptors, Natural Killer Cell
- Receptors, Immunologic
- Proto-Oncogene Proteins c-vav
- Proto-Oncogene Proteins
- Protein-Tyrosine Kinases