Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 12, Pages 8625-8632Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.12.8625
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Funding
- NHLBI NIH HHS [P01 HL57345] Funding Source: Medline
- NIGMS NIH HHS [R01GM3273, R01 GM032373] Funding Source: Medline
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The siglecs (Sialic acid-binding immunoglobulin superfamily lectins) are immunoglobulin superfamily members recognizing sialylated ligands, Most prior studies of siglec specificities focused on alpha 2-3- and alpha 2-6-sialyllactos(amin)es and on one or two of the siglecs at a time. Here, we explore several new aspects of specificities of the first six reported siglecs, using sialylated glycans presented in multivalent form, on synthetic polyacrylamide backbones, or on mucin polypeptides. First, me report that binding of siglec-1 (sialoadhesin), siglec-3 (CD33), siglec-4a (myelin-associated glycoprotein), and siglec-5 to alpha 2-3 sialyllactosamine is affected markedly by the presence of an alpha 1-3-linked fucose. Thus, while siglecs may not interfere with selectin-mediated recognition, fucosylation could negatively regulate siglec binding. Second, in contrast to earlier studies, we find that siglec-3 prefers alpha 2-6-sialyllactose, Third, siglec-5 binds alpha 2-8-linked sialic acid, making it the siglec least specific for linkage recognition. Fourth, siglecs-2 (CD22), -3, -5, and -6 (obesity-binding protein 1) showed significant binding to sialyl-Tn (Neu5Ac alpha 2-6-GalNAc), a tumor marker associated with poor prognosis. Fifth, siglec-6 is an exception among siglecs in not requiring the glycerol side chain of sialic acid for recognition. Sixth, all siglecs require the carboxyl group of sialic acid for binding, Finally, the presentation of the sialyl-Tn epitope and/or more extended structures that include this motif may be important for optimal recognition by the siglecs, This was concluded from studies using ovine, bovine, and porcine submaxillary mucins and Chinese hamster ovary cells transfected with ST6GalNAc-I and/or the mucin polypeptide MUC1.
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