A new siglec family member, siglec-10, is expressed in cells of the immunesystem and has signaling properties similar to CD33

Citation
G. Whitney et al., A new siglec family member, siglec-10, is expressed in cells of the immunesystem and has signaling properties similar to CD33, EUR J BIOCH, 268(23), 2001, pp. 6083-6096
Citations number
41
Categorie Soggetti
Biochemistry & Biophysics
Journal title
EUROPEAN JOURNAL OF BIOCHEMISTRY
ISSN journal
00142956 → ACNP
Volume
268
Issue
23
Year of publication
2001
Pages
6083 - 6096
Database
ISI
SICI code
0014-2956(200112)268:23<6083:ANSFMS>2.0.ZU;2-M
Abstract
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 19q13.3-4 that encode other siglec family members. We have demonstrated that siglec-10 is an immu ne system-restricted membrane-bound protein that is highly expressed in per ipheral blood leukocytes as demonstrated by Northern, RT-PCR and flow cytom etry. 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-si gnaling motifs (Y597 and Y667) and are likely involved in intracellular sig naling. The ability of tyrosine kinases to phosphorylate the cytoplasmic ty rosines was evaluated by kinase assay using wild-type siglec-10 cytoplasmic domain and Y -->F mutants. The majority of the phosphorylation could be at tributed to Y597 and Y667. Further experiments with cell extracts suggest t hat Src homology region 2 domain-containing protein tyrosine phosphatase (S HP)-1 interacts with Y667 and SHP-2 interacts with Y667 in addition to anot her tyrosine. This is very similar to CD33, which also binds the phosphatas es SHP-1 and SHP-2, therefore siglec-10, as CD33, may be characterized as a n inhibitory receptor.