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PMID:14662855

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Citation

Chung, DH, Humphrey, MB, Nakamura, MC, Ginzinger, DG, Seaman, WE and Daws, MR (2003) CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. J. Immunol. 171:6541-8

Abstract

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.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Antigens, Surface/chemistry; Cell Differentiation/immunology; Cell Line; Cell Line, Tumor; Cloning, Molecular; Growth Inhibitors/chemistry; Growth Inhibitors/genetics; Growth Inhibitors/physiology; Immunoglobulins/chemistry; Intracellular Signaling Peptides and Proteins; Leukemia P388; Membrane Glycoproteins/chemistry; Membrane Proteins/chemistry; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Multigene Family/immunology; Myeloid Cells/metabolism; Osteoclasts/cytology; Osteoclasts/immunology; Protein Phosphatase 1; Protein Structure, Tertiary; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases/metabolism; Receptors, Immunologic/biosynthesis; Receptors, Immunologic/chemistry; Receptors, Immunologic/genetics; Receptors, Immunologic/physiology; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TNF11

acts_upstream_of_or_within

GO:0030316: osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHPS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q6SJQ7

F

Seeded From UniProt

complete

MOUSE:CLM1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97797

F

Seeded From UniProt

complete

MOUSE:CLM1

acts_upstream_of_or_within

GO:0030316: osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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