tailieunhanh - Báo cáo Y học: A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to CD33

The siglecs (sialic acid-binding Ig-like lectins) are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome that encode other siglec family members. We have demonstrated that siglec-10 is an immune systemrestricted. | Eur. J. Biochem. 268 6083-6096 2001 FEBS 2001 A new siglec family member siglec-10 is expressed in cells of the immune system and has signaling properties similar to CD33 Gena Whitney1 Shulin Wang1 Han Chang2 Ke-Yi Cheng1 Pin Lu1 Xia D. Zhou1 Wen-Pin Yang2 Murray McKinnon1 and Malinda Longphre1 1 Inflammation and Pulmonary Drug Discovery Department and 2Applied Genomics Department Bristol-Myers Squibb Pharmaceutical Research Institute Princeton NJ USA The siglecs sialic acid-binding Ig-like lectins are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains a transmembrane domain and a cytoplasmic tail containing two ITIM-signaling motifs. Siglec-10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome that encode other siglec family members. We have demonstrated that siglec-10 is an immune system-restricted membrane-bound protein that is highly expressed in peripheral blood leukocytes as demonstrated by Northern RT-PCR and flow cytometry. Binding assays determined that the extracellular domain of siglec-10 was capable of binding to peripheral blood leukocytes. The cytoplasmic tail of siglec-10 contains four tyrosines two of which are embedded in ITIM-signaling motifs Y597 and Y667 and are likely involved in intracellular signaling. The ability of tyrosine kinases to phosphorylate the cytoplasmic tyrosines was evaluated by kinase assay using wild-type siglec-10 cytoplasmic domain and Y F mutants. The majority of the phosphorylation could be attributed to Y597 and Y667. Further experiments with cell extracts suggest that Src homology region 2 domain-containing protein tyrosine phosphatase SHP -1 interacts with Y667 and SHP-2 interacts with Y667