KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions.
The signaling adaptor protein KARAP/DAP12/TYROBP (killer cell activating receptor-associated protein / DNAX activating protein of 12 kDa / tyrosine kinase binding protein) belongs to the family of transmembrane polypeptides bearing an intracytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). This adaptor, initially characterized in NK cells, is associated with multiple cell-surface activating receptors expressed in both lymphoid and myeloid lineages. We review here the main features of KARAP/DAP12, describing findings from its identification to recently published data, showing its involvement in a broad array of biological functions. KARAP/DAP12 is a wiring component for NK cell anti-viral function (e.g. mouse cytomegalovirus via its association with mouse Ly49H) and NK cell anti-tumoral function (e.g. via its association with mouse NKG2D or human NKp44). KARAP/DAP12 is also involved in inflammatory reactions via its coupling to myeloid receptors, such as the triggering receptors expressed by myeloid cells (TREM) displayed by neutrophils, monocytes/macrophages and dendritic cells. Finally, bone remodeling and brain function are also dependent upon the integrity of KARAP/DAP12 signals, as shown by the analysis of KARAP/DAP12-deficient mice and KARAP/DAP12-deficient Nasu-Hakola patients.
Tomasello
Elena
E
Laboratory of NK cells and Innate Immunity, Centre d'Immunologie de Marseille-Luminy, INSERM - CNRS - Université de la Méditerranée, Marseille, France. tomasello@ciml.univ-mrs.fr
Vivier
Eric
E
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016723:Bone Remodeling; D001921:Brain / Q000473:pathology; D019070:Cell Lineage; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human