Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes.
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.
Marshall
Andrew S J
AS
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Willment
Janet A
JA
Lin
Hsi-Hsien
HH
Williams
David L
DL
Gordon
Siamon
S
Brown
Gordon D
GD
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D016466:CHO Cells; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D006031:Glycosylation; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010802:Phylogeny; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011973:Receptors, LDL / Q000737:chemistry; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C485220:CLEC12A protein, human; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011973:Receptors, LDL; D011975:Receptors, Mitogen; D014409:Tumor Necrosis Factor-alpha; D012313:RNA