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Publication : Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D.

First Author  Diefenbach A Year  2002
Journal  Nat Immunol Volume  3
Issue  12 Pages  1142-9
PubMed ID  12426565 Mgi Jnum  J:219772
Mgi Id  MGI:5629693 Doi  10.1038/ni858
Citation  Diefenbach A, et al. (2002) Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol 3(12):1142-9
abstractText  Optimal lymphocyte activation requires the simultaneous engagement of stimulatory and costimulatory receptors. Stimulatory immunoreceptors are usually composed of a ligand-binding transmembrane protein and noncovalently associated signal-transducing subunits. Here, we report that alternative splicing leads to two distinct NKG2D polypeptides that associate differentially with the DAP10 and KARAP (also known as DAP12) signaling subunits. We found that differential expression of these isoforms and of signaling proteins determined whether NKG2D functioned as a costimulatory receptor in the adaptive immune system (CD8+ T cells) or as both a primary recognition structure and a costimulatory receptor in the innate immune system (natural killer cells and macrophages). This strategy suggests a rationale for the multisubunit structure of stimulatory immunoreceptors.
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