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J Biol Chem, Vol. 273, Issue 51, 34115-34119, December 18, 1998

Gene Structure, Expression Pattern, and Biological Activity of Mouse Killer Cell Activating Receptor-associated Protein (KARAP)/DAP-12

Elena TomaselloDagger , Lucia OlceseDagger , Frédéric VélyDagger , Christophe Geourgeon§, Mathieu BléryDagger , Aziz MoqrichDagger , Daniel Gautheret, Malek DjabaliDagger , Marie-Geneviève Matteiparallel , and Eric VivierDagger **

From the Dagger  Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, Case 906, 13288 Marseille cedex 09, France, the § IBCP, CNRS UPR 412, 69 367 Lyon cedex 07, France, the  CNRS, E.P.91, 13402 Marseille cedex 20, France, the parallel  INSERM U491, Faculté de Médecine de la Timone, Marseille, France, and the ** Institut Universitaire de France, Paris, 75005 France

Natural killer cell and T cell subsets express at their cell surface a repertoire of receptors for MHC class I molecules, the natural killer cell receptors (NKRs). NKRs are characterized by the existence of inhibitory and activating 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 isoforms lack any immunoreceptor tyrosine-based inhibition motif but harbor a charged amino acid residue in their transmembrane domain. We previously characterized 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 organization in five exons. Point mutation and transfection studies revealed that KARAP is a novel signaling transmembrane subunit whose transduction function depends on the integrity of an intracytoplasmic immunoreceptor tyrosine-based 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 association with a broad range of activating receptors in a variety of tissues.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.


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