背景 | CD300f, also known as CD300LF, LMIR3, IREM-1, CLM-1, IgSF13, DIgR1, and MAIR-V, is a 50‑60 kDa glycoprotein member of the immunoglobulin superfamily (1). Human CD300f consists of a 137 amino acid (aa) extracellular domain (ECD) with one Ig-like V-type domain, a 21 aa transmembrane segment, and a 113 aa cytoplasmic domain that contains multiple immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or ITIM-like sequences (2, 3). Alternate splicing generates additional isoforms that carry substituted C-terminal tails of varying lengths and sequences following the ECD or transmembrane segment (3). Within the ECD, human CD300f shares 43% aa sequence identity with mouse and rat CD300f. CD300f is expressed on the surface of dendritic cells, monocytes, granulocytes, and mast cells as well as on acute myeloid leukemia (AML) blasts (2-4). Pervanadate treatment or antibody crosslinking of CD300f induces phosphorylation of tyrosine residues in the cytoplasmic domain and the subsequent recruitment of phosphatases SHIP, SHP-1, SHP-2, and the p85 alpha subunit of PI3K (2, 3, 5, 6). CD300f ligation can induce cell death and inhibit signaling through multiple receptors including Fc epsilon RI, LMIR4, SCF R, TLR2, TLR3, and TLR9 (3-8). In contrast, it enhances TLR4-mediated signaling/cytokine production in mast cells through association with the activating signaling protein FcR gamma (5). In mouse, a splice variant of CD300f (known as DIgR2, with a 7 aa insertion in the ECD) inhibits CD4+ T cell activation and in vivo Th1 and CTL responses (9). CD300f is upregulated on monocytes surrounding experimentally-induced spinal cord demyelination and functions as a negative regulator of inflammation in the CNS (10). |
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