mSiglec-E, a novel mouse CD33-related siglec (sialic acid-binding immunoglobulin-like lectin) that recruits Src homology 2 (SH2)-domain-containing protein tyrosine phosphatases SHP-1 and SHP-2

The sialic acid-binding immunoglobulin-like lectins (siglecs) represent a r ecently defined distinct subset of the immunoglobulin superfamily. By using the Src homology 2 (SH2)-domain-containing protein tyrosine phosphatase SH P-1 as bait in a yeast two-hybrid screen, we have identified a new member o f the mouse siglec family, mSiglec-E. The mSiglec-E cDNA encodes a protein of 467 amino acids that contains three extracellular immunoglobulin-like do mains, a transmembrane region and a cytoplasmic tail bearing two immunorece ptor tyrosine-based inhibitory motifs (ITIMs). mSiglec-E is highly expresse d in mouse spleen, a tissue rich in leucocytes. The ITIMs of mSiglec-E can recruit SHP-1 and SHP-2, two inhibitory regulators of immunoreceptor signal transduction. This suggests that the function of mSiglec-E is probably an involvement in haematopoietic cells and the immune system as an inhibitory receptor. When expressed in COS-7 cells, mSiglec-E was able to mediate sial ic acid-dependent binding to human red blood cells, suggesting that mSiglec -E may function through cell-cell interactions. In comparison with the know n members of the siglec family, mSiglec-E exhibits a high degree of sequenc e similarity to both human siglec-7 and siglec-9. The gene encoding mSiglec -E is localized in the same chromosome as that encoding mouse CD33. Phyloge netic analysis reveals that neither mouse mSiglec-E nor CD33 shows a clear relationship with any human siglecs so far identified.