Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes

Andrew S. J. Marshall, Janet Anne Willment, Hsi-Hsien Lin, David L. Williams, Siamon Gordon, Gordon Douglas Brown

Research output: Contribution to journalArticle

102 Citations (Scopus)

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 languageEnglish
Pages (from-to)14792-14802
Number of pages11
JournalThe Journal of Biological Chemistry
Volume279
Issue number15
DOIs
Publication statusPublished - 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

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