Abstract
Inhibitory and activatory C-type lectin-like receptors play an important role in immunity through the regulation of leukocytes. Here, we report the identification and characterization of a novel myeloid inhibitory C-type lectin-like receptor (MICL) whose expression is primarily restricted to granulocytes and monocytes. This receptor, which contains a single C-type lectin-like domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, is related to LOX-1 (lectin-like receptor for oxidized low density lipoprotein-1) and the beta-glucan receptor (Dectin-1) and is variably spliced and highly N-glycosylated. We demonstrate that it preferentially associates with the signaling phosphatases SHP-1 and SHP-2, but not with SHIP. Novel chimeric analyses with a construct combining MICL and the beta-glucan receptor show that MICL can inhibit cellular activation through its cytoplasmic immunoreceptor tyrosine-based inhibitory motif. These data suggest that MICL is a negative regulator of granulocyte and monocyte function.
Original language | English |
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Pages (from-to) | 14792-14802 |
Number of pages | 11 |
Journal | The Journal of Biological Chemistry |
Volume | 279 |
Issue number | 15 |
DOIs | |
Publication status | Published - 9 Apr 2004 |
Keywords
- alternative splicing
- amino acid motifs
- amino acid sequence
- animals
- base sequence
- blotting, Northern
- CHO cells
- cell line
- cloning, molecular
- Cricetinae
- cytoplasm
- glycosylation
- granulocytes
- humans
- lectins, C-type
- mice
- models, biological
- molecular sequence data
- monocytes
- NIH 3T3 Cells
- phylogeny
- precipitin tests
- protein binding
- protein structure, tertiary
- RNA
- messenger RNA
- rats
- LDL receptors
- mitogen receptors
- reverse transcriptase polymerase chain reaction
- sequence homology, amino acid
- signal transduction
- fluorescence spectrometry
- tissue distribution
- transfection
- tumor necrosis factor-alpha