CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation.
By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse expressed sequence tag database and isolated a new single Ig domain receptor, which we have expressed and characterized. The receptor is most similar in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like ... molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was part of a multigene family located on a small segment of mouse chromosome 11. Each contains a single Ig domain, and they are expressed mainly in cells of the myeloid lineage. CLM-1 contains multiple cytoplasmic tyrosine residues, including two that lie in consensus immunoreceptor tyrosine-based inhibitory motifs, and we demonstrate that CLM-1 can associate with Src-homology 2 containing phosphatase-1. Expression of CLM-1 mRNA is down-regulated by treatment with receptor activator of NF-kappaB ligand (RANKL), a cytokine that drives osteoclast formation. Furthermore, expression of CLM-1 in the osteoclastogenic cell line RAW (RAW.CLM-1) prevents osteoclastogenesis induced by RANKL and TGF-beta. RAW.CLM-1 cells fail to multinucleate and do not up-regulate calcitonin receptor, but they express tartrate-resistant acid phosphatase, cathepsin K, and beta(3) integrin, suggesting that osteoclastogenesis is blocked at a late-intermediate stage. Thus, we define a new family of myeloid receptors, and demonstrate that the first member of this family, CLM-1, is an inhibitory receptor, able to block osteoclastogenesis.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, Surface, Cell Differentiation, Cell Line, Cell Line, Tumor, Cloning, Molecular, Growth Inhibitors, Immunoglobulins, Intracellular Signaling Peptides and Proteins, Leukemia P388, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Multigene Family, Myeloid Cells, Osteoclasts, Protein Phosphatase 1, Protein Structure, Tertiary, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Immunologic, Sequence Homology, Amino Acid
Amino Acid Sequence, Animals, Antigens, Surface, Cell Differentiation, Cell Line, Cell Line, Tumor, Cloning, Molecular, Growth Inhibitors, Immunoglobulins, Intracellular Signaling Peptides and Proteins, Leukemia P388, Membrane Glycoproteins, Membrane Proteins, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Multigene Family, Myeloid Cells, Osteoclasts, Protein Phosphatase 1, Protein Structure, Tertiary, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Immunologic, Sequence Homology, Amino Acid
J. Immunol.
Date: Dec. 15, 2003
PubMed ID: 14662855
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