Major O‐glycosylated sialoglycoproteins of human hematopoietic cells: Differentiation antigens with poorly understood functions

Abstract

All human hematopoietic cells seem to contain a major, heavily O-glycosylated sialoglycoprotein. Glycophorin A is specific for the erythroid lineage of cells, and leukocytes have a major sialoglycoprotein, also called leukosialin or sialophorin. Cell differentiation results in patterns of O-glycosylation in these proteins, which reflect the stage of differentiation within a cell lineage as well as lineage specificity. The altered carbohydrate compositions may influence the interactions of the cells with external ligands. Healthy individuals lacking glycophorin A in their red cells are known, whereas a deficiency of the leukocyte sialoglycoprotein may result in immunological disease. Although little is known about the physiological functions of these proteins, they form interesting models for studies on regulation of glycosylation, biosynthesis of O-glycosylated glycoproteins, and function of cell surface receptors.

The Tn Antigen—Structural Simplicity and Biological Complexity

“…These complex O ‐glycans usually have extended structures based on core 1 or core 2 O ‐glycans and are found in numerous cell‐surface glycoproteins. Glycoproteins containing core 1 or 2 O ‐glycans include the low‐density‐lipoprotein (LDL) receptor,136–138 the transferrin receptor,129, 139–141 glycophorin A,142–144 podoplanin,145–147 PSGL‐1,30, 148–150 CD34,151 endoglycan,152 zona pellucida glycoprotein ZP3,153, 154 CD43,155–157 CD45,158–161 the TRAIL receptor family,162 the neurotrophin receptor,163, 164 the MUC family of mucins (both membrane‐bound and secreted),165–169 platelet glycoprotein GPIbα,170 and platelet integrin GPIIb/IIIa (αIIbβ3) 171. Such core 1 and/or 2 O ‐glycans are also found in many secreted and serum glycoproteins, including human IgA1172–177 and IgD,178–180 erythropoietin,181–184 von Willebrand factor (vWF),185 blood coagulation factor X,186 serum apoC‐III,187–189 human chorionic gonadotropin (HCG),190–193 interleukin‐6 (IL‐6),194, 195 Tamm–Horsfall glycoprotein/uromodulin,196–199 Gc macrophage activating factor (GcMAF, a naturally derived form of human vitamin D binding protein),200 human urinary thrombomodulin,201 and human milk bile‐salt‐stimulated lipase 202–205.…”

3'-Azidothymidine potently Inhibits the biosynthesis of highly branched N-linked oligosaccharides and poly-N-acetyllactosamine chains in cells

“…(8). Several other developmentally regulated events including increases in O-linked glycosylation, changes in proteoglycan expression and altered glycosphingolipid metabolism also occur concomitant with the maturation of many hematopoietic stem cells (9)(10)(11)(12). While the precise role of these changes have not been completely elucidated, the remodeling of surface oligosaccharides by inhibitors of glycosylation may compromise the ability of these cells to proliferate and differentiate by altering specific structural determinants crucial for cell-cell interactions and signal transduction events.…”

Tn and sialyl‐Tn antigens, aberrant O‐glycomics as human disease markers

“…O ‐glycans play important roles in many biological processes, such as signal transduction, cell–cell interaction (selectins and their ligands), immunity, and angiogenesis . The core 1 O ‐glycan is the most common core structure in normal glycoproteins of the endothelium and of hematopoietic cells, including erythrocytes and leukocytes . Epithelial cells of the GI tract also form core 1 structures, but can alternatively modify the Tn antigen to form the core 3 structure (GlcNAcβ1,3GalNAc‐α‐Ser/Thr) by the action of core 3 β1,3 N ‐acetylglucosaminyltransferase (core 3 GnT, C3GnT, β3GnT‐6).…”