Abstract
Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF-alpha production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adult
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Amino Acid Sequence
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Animals
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Antigens, Surface / chemistry
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Antigens, Surface / genetics
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Base Sequence
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COS Cells
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Cell Differentiation / immunology
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Cell Line, Tumor
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Cell Lineage / genetics
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Cell Lineage / immunology
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Chlorocebus aethiops
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Cloning, Molecular / methods
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Down-Regulation / immunology
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Female
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HL-60 Cells
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Humans
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Jurkat Cells
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K562 Cells
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Proteins
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Monocytes / cytology
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Monocytes / immunology*
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Monocytes / metabolism*
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NFATC Transcription Factors
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Rats
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Receptors, Immunologic / antagonists & inhibitors
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / chemistry*
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Receptors, Immunologic / genetics*
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Receptors, Immunologic / metabolism
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transfection
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U937 Cells
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Surface
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CD300C protein, human
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DNA-Binding Proteins
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Membrane Glycoproteins
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Membrane Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Receptors, Immunologic
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TYROBP protein, human
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Transcription Factors