Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family

Eur J Immunol. 2001 Mar;31(3):783-91. doi: 10.1002/1521-4141(200103)31:3<783::aid-immu783>;2-u.


The presence of a negatively charged residue in the transmembrane domain of DAP12 precludes its cell surface expression in the absence of a partner receptor containing a positive charge in its transmembrane domain. We utilized this property of DAP12 to screen a BALB / c macrophage cDNA library for novel molecules that induce cell surface expression of DAP12. By this method, we cloned a cell surface receptor with a single Ig (V) domain, a transmembrane lysine residue, and a short cytoplasmic domain. By homology screening of BALB / c macrophage libraries, we identified a second cDNA for a highly homologous receptor. These receptors appear to be the mouse orthologues of a recently identified human cDNA, TREM-2, so we have designated the receptors as mouse TREM-2a and TREM-2b. By Northern blotting, transcripts for TREM-2 were found in each of three macrophage cell lines but not in a variety of other hematopoietic cell lines. We further demonstrate that TREM-2a is associated with endogenous DAP12 in macrophage cells, and cross-linking of TREM-2a on the surface of macrophages leads to the release of nitric oxide. Our studies define TREM-2 as a receptor family in mouse macrophages and demonstrate the capacity of these receptors to activate macrophage function through DAP12.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cloning, Molecular
  • Humans
  • Immunoglobulins / genetics
  • Macrophages / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Nitric Oxide / biosynthesis
  • Phylogeny
  • Protein Structure, Tertiary
  • RNA, Messenger / biosynthesis
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism*
  • Sequence Homology, Amino Acid


  • Adaptor Proteins, Signal Transducing
  • Immunoglobulins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • TREM-2a receptor
  • TREM-2b receptor
  • TYROBP protein, human
  • Nitric Oxide

Associated data

  • GENBANK/AY024348
  • GENBANK/AY024349