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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.

Pubmed ID: 14662855

Authors

  • Chung DH
  • Humphrey MB
  • Nakamura MC
  • Ginzinger DG
  • Seaman WE
  • Daws MR

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

December 15, 2003

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA87922-01A1

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