Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12

Natural killer cell and T cell subsets express at their cell surface a repe rtoire of receptors for MHC class I molecules, the natural killer cell rece ptors (NKRs), NKRs are characterized by the existence of inhibitory and act ivating isoforms, which are encoded by highly homologous but separate genes present in the same locus. Inhibitory isoforms express an intracytoplasmic immunoreceptor tyrosine-based inhibition motif, whereas activating isoform s lack any immunoreceptor tyrosine-based inhibition motif but harbor a char ged amino acid residue in their transmembrane domain. We previously charact erized KARAP (killer cell activating receptor-associated protein), a novel disulfide-linked tyrosine-phosphorylated dimer that selectively associates with the activating NKR isoforms. We report here the identification of the mouse KARAP gene, its localization on chromosome 7 and its genomic organiza tion in five exons. Point mutation and transfection studies revealed that K ARAP is a novel signaling transmembrane subunit whose transduction function depends on the integrity of an intracytoplasmic immunoreceptor tyrosine-ba sed activation motif. In contrast to previous members of the immunoreceptor tyrosine-based activation motif polypeptide family, KARAP is ubiquitously expressed on hematopoietic and nonhematopoietic cells, suggesting its assoc iation with a broad range of activating receptors in a variety of tissues.