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
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.