An activating immunoreceptor complex formed by NKG2D and DAP10

Science. 1999 Jul 30;285(5428):730-2. doi: 10.1126/science.285.5428.730.

Abstract

Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Cytotoxicity, Immunologic
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Ligands
  • Lymphocyte Activation*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms / immunology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Natural Killer Cell
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • src Homology Domains

Substances

  • HCST protein, human
  • Hcst protein, mouse
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Phosphotyrosine
  • Phosphatidylinositol 3-Kinases

Associated data

  • GENBANK/AF072844
  • GENBANK/AF072845
  • GENBANK/AF072846
  • GENBANK/AF122904
  • GENBANK/AF122905