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Biomedical subjects

A Varki

Publications and source records attributed to A Varki.

At least 55 records · Page 3Linked to original sources
PubMed1998

Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes.

CD22 is a B cell-restricted glycoprotein involved in signal transduction and modulation of cellular activation. It is also an I-type lectin (now designated Siglec-2), whose extracellular domain can specifically recognize alpha2-6-linked sialic acid (Sia) residues. This activity is postulated to mediate intercellular adhesion and/or to act as a coreceptor in antigen-induced B cell activation. However, studies with recombinant CD22 indicate that the lectin function can be inactivated by expression of alpha2-6-linked Sia residues on the same cell surface. To explore whether this masking phenomenon affects native CD22 on B cells, we first developed a probe to detect the lectin activity of recombinant CD22 expressed on Chinese hamster ovary cells (which have no endogenous alpha2-6-linked Sia residues). This probe is inactive against CD22-positive B lymphoma cells and Epstein-Barr virus-transformed lymphoblasts which express high levels of alpha2-6-linked Sia residues. Enzymatic desialylation unmasks the CD22 lectin activity, indicating that endogenous Sia residues block the CD22 lectin-binding site. Truncation of the side chains of cell surface Sia residues by mild periodate oxidation (known to abrogate Sia recognition by CD22) also had this unmasking effect, indicating that the effects of desialylation are not due to a loss of negative charge. Normal resting B cells from human peripheral blood gave similar findings. However, the lectin is partially unmasked during in vitro activation of these cells. Thus, the lectin activity of CD22 is restricted by endogenous sialylation in resting B cells and may be transiently unmasked during in vivo activation, perhaps to modulate intercellular or intracellular interactions at this critical stage in the humoral response.

Animals↗
PubMed1998

Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low molecular weight heparins as therapeutic agents.

The selectins are calcium-dependent C-type lectins that bind certain sialylated, fucosylated, sulfated glycoprotein ligands. L-selectin also recognizes endothelial proteoglycans in a calcium-dependent manner, via heparan sulfate (HS) glycosaminoglycan chains enriched in unsubstituted glucosamine units. We now show that these HS chains can also bind P-selectin, but not E-selectin. However, while L-selectin binding requires micromolar levels of free calcium, P-selectin recognition is largely divalent cation-independent. Despite this, HS chains bound to P-selectin are eluted by ethylenediamine tetraacetic acid (EDTA), but only at high concentrations. Porcine intestinal mucosal (mast cell-derived) heparin (PIM-heparin) shows similar properties, with no binding to E-selectin, calcium-dependent binding of a subfraction to L-selectin and to P-selectin, and calcium-independent binding of a larger fraction to P-selectin, the latter being disrupted by high EDTA concentrations. Analysis of defined heparin fragment pools shows a size dependence for interaction, with tetradecasaccharides showing easily detectable binding to L- and P-selectin affinity columns. L-selectin binding fragments include more heavily sulfated and epimerized regions and, as with the endothelial HS chains, they are enriched in free amino groups. The P-selectin binding component includes this fraction as well as some less highly modified regions. Thus, endothelium-derived HS chains and mast cell-derived heparins could play a role in modulating the biology of selectins in vivo. Notably, P- and L-selectin binding to sialyl-Lewisx and to HL-60 cells (which are known to carry the native ligand PSGL-1) is inhibited by unfractionated pharmaceutical heparin preparations at concentrations 12-50-fold lower than those recommended for effective anticoagulation in vivo. In contrast, two low molecular weight heparins currently considered as clinical replacements for unfractionated heparin are much poorer inhibitors. Thus, patients undergoing heparin therapy for other reasons may be experiencing clinically significant inhibition of L- and P-selectin function, and the current switchover to low-molecular weight heparins may come at some loss of this effect. Low-dose unfractionated heparin should be investigated as a treatment option for acute and chronic diseases in which P- and L-selectin play pathological roles.

Animals↗
PubMed1998

A structural difference between the cell surfaces of humans and the great apes.

The sialic acids are major components of the cell surfaces of animals of the deuterostome lineage. Earlier studies suggested that humans may not express N-glycolyl-neuraminic acid (Neu5Gc), a hydroxylated form of the common sialic acid N-acetyl-neuraminic acid (Neu5Ac). We find that while Neu5Gc is essentially undetectable on human plasma proteins and erythrocytes, it is a major component in all the four extant great apes (chimpanzee, bonobo, gorilla and orangutan) as well as in many other mammals. This marked difference is also seen amongst cultured lymphoblastoid cells from humans and great apes, as well as in a variety of other tissues compared between humans and chimpanzees, including the cerebral cortex and the cerebrospinal fluid. Biosynthetically, Neu5Gc arises from the action of a hydroxylase that converts the nucleotide donor CMP-Neu5Ac to CMP-Neu5Gc. This enzymatic activity is present in chimpanzee cells, but not in human cells. However, traces of Neu5Gc occur in some human tissues, and others have reported expression of Neu5Gc in human cancers and fetal tissues. Thus, the enzymatic capacity to express Neu5Gc appears to have been suppressed sometime after the great ape-hominid divergence. As terminal structures on cell surfaces, sialic acids are involved in intercellular cross-talk involving specific vertebrate lectins, as well as in microbe-host recognition involving a wide variety of pathogens. The level of sialic acid hydroxylation (level of Neu5Ac versus Neu5Gc) is known to positively or negatively affect several of these endogenous and exogenous interactions. Thus, there are potential functional consequences of this widespread structural change in humans affecting the surfaces of cells throughout the body.

Animals↗
PubMed1998

Factors controlling the glycosylation potential of the Golgi apparatus.

Most of the biosynthetic reactions that generate the oligosaccharide structures of eukaryotic cells occur in compartments of the Golgi apparatus. This article provides a brief outline of the major glycosylation pathways of the Golgi, and discusses current understanding of the many factors that can control the glycosylation potential of this organelle. Old and new approaches towards elucidating the organization of glycosylation machinery in the Golgi are also considered.

Animals↗
PubMed1998

Induction of sialic acid 9-O-acetylation by diverse gene products: implications for the expression cloning of sialic acid O-acetyltransferases.

Sialic acids can be modified by O-acetyl esters at the 7- and/or 9-position, altering recognition by antibodies, lectins and viruses. 9(7)-O-acetylation is mediated by a sialic acid-specific O-acetyltransferase, which has proven difficult to purify. Two groups have recently isolated cDNAs possibly encoding this enzyme, by expression cloning of human melanoma libraries in COS cells expressing the substrate ganglioside GD3. Pursuing a similar approach, we have isolated additional clones that can induce 9-O-acetylation. One clone present in a melanoma library encodes a fusion protein between a bacterial tetracycline resistance gene repressor and a sequence reported to be part of the P3 plasmid. Expression of the open reading frame is necessary for inducing 9-O-acetylation, indicating that this is not a reaction to the introduction of bacterial DNA. Another clone from a rat liver cDNA library induced 9-O-acetylation on COS cells expressing alpha2-6-linked sialic acids, and encodes an open reading frame identical to the Vitamin D binding protein. However, truncation at the 5' end eliminates the amino-terminal hydrophobic signal sequence, predicting cytosolic hyperexpression of a truncated protein. Thus, diverse types of cDNAs can indirectly induce sialic acid 9-O-acetylation in the COS cell system, raising the possibility that the real enzyme may be composed of multiple subunits which would not be amenable to expression cloning. Importantly, the cDNAs we isolated are highly specific in their ability to induce 9-O-acetylation either on alpha2-6-linked sialic acids of glycoproteins (truncated vitamin D binding protein) or on the alpha2-8-linked sialic acids of gangliosides (Tetrfusion protein). These data confirm our prior suggestion that a family of O-acetyltransferases with distinctive substrate specificities exists in mammalian systems.

Acetylation↗
PubMed1998

Inhibition of L- and P-selectin by a rationally synthesized novel core 2-like branched structure containing GalNAc-Lewisx and Neu5Acalpha2-3Galbeta1-3GalNAc sequences.

The selectins interact in important normal and pathological situations with certain sialylated, fucosylated glycoconjugate ligands containing sialyl Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone into the synthesis of sialylated and sulfated Lewisxanalogs as competitive ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure, we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++ +-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies have shown that sulfate esters can replace sialic acid in some selectin ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. , Nature, 361, 555, 1993). Based upon these observations, we hypothesized that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of interacting with L- and P-selectin. To examine this hypothesis, we synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++ +-3Galbeta1-3)-GalNAc alpha1-OB, which was found to be 2- to 3-fold better than sialyl Lexfor P and L selectin, respectively. We also report the synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1- 3)GlcNAcbeta1-OMe (GalNAc-Lewisx-O-methyl glycoside), which also proved to be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe. Combining this with our knowledge of Core 2 branched structures, we have synthesized a molecule that is 5- to 6-fold better at inhibiting L- and P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures, substitution of a sulfate ester group for a sialic acid residue in such a molecule resulted in a considerable loss of inhibition ability. Thus, the combination of a sialic acid residue on the primary (beta1-3) arm, and a modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2 structure generated a monovalent synthetic oliogosaccharide inhibitor superior to SLexfor both L- and P-selectin.

Binding, Competitive↗
PubMed1997

An IgG monoclonal antibody against Dictyostelium discoideum glycoproteins specifically recognizes Fucalpha1,6GlcNAcbeta in the core of N-linked glycans. Localized expression of core-fucosylated glycoconjugates in human tissues.

Core fucosylation of N-linked oligosaccharides (GlcNAcbeta1, 4(Fucalpha1,6)GlcNAcbeta1-Asn) is a common modification in animal glycans, but little is known about the distribution of core-fucosylated glycoproteins in mammalian tissues. Two monoclonal antibodies, CAB2 and CAB4, previously raised against carbohydrate epitopes of Dictyostelium discoideum glycoproteins (Crandall, I. E. and Newell, P. C. (1989) Development 107, 87-94), specifically recognize fucose residues in alpha1,6-linkage to the asparagine-bound GlcNAc of N-linked oligosaccharides. These IgG3 antibodies do not cross-react with glycoproteins containing alpha-fucoses in other linkages commonly seen in N- or O-linked sugar chains. CAB4 recognizes core alpha1,6 fucose regardless of terminal sugars, branching pattern, sialic acid linkage, or polylactosamine substitution. This contrasts to lentil and pea lectins that recognize a similar epitope in only a subset of these structures. Additional GlcNAc residues found in the core of N-glycans from dominant Chinese hamster ovary cell mutants LEC14 and LEC18 progressively decrease binding. These antibodies show that many proteins in human tissues are core-fucosylated, but their expression is localized to skin keratinocytes, vascular and visceral smooth muscle cells, epithelia, and some extracellular matrix-like material surrounding subpopulations of lymphocytes. The availability of these antibodies now allows for an extended investigation of core fucose epitope expression in development and malignancy and in genetically manipulated mice.

Animals↗
PubMed1997

9-O-Acetylation of sialomucins: a novel marker of murine CD4 T cells that is regulated during maturation and activation.

Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8-10% carry 9-O-acetylation; the great majority of these are the more mature PNA-, HSA-, and TCRhi medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80- 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90-95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)hi, features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation.

Acetylation↗
PubMed1997

Selectin inhibition: synthesis and evaluation of novel sialylated, sulfated and fucosylated oligosaccharides, including the major capping group of GlyCAM-1.

Selectins interact with glycoconjugate ligands in important normal and pathological situations. While high affinity recognition of natural ligands is associated with alpha 1-3(4)fucosylated, alpha 2-3sialylated (and/or sulfated) lactosamine sequences, small oligosaccharides that potently inhibit the selectins have not been found. One possibility suggested by other investigators is that high affinity may require unusual sequences not yet tested, for example, the "major capping group" (6'-sulfo-sialyl Le(x)) of the L-selectin ligand GlyCAM-1. To explore this possibility, we synthesized a spectrum of novel synthetic and semisynthetic oligosaccharides related to those on natural ligands. In studying these molecules, we noted that binding of recombinant soluble selectins to immobilized sialyl Le(a) or 3'-sulfo-Le(x) is markedly inhibited by concentrations of chloride above the physiological range. This indicates the ionic nature of the interactions, and shows that buffers typically used in screening assays for inhibitors are not optimal. Using parameters that more closely approximate physiological conditions, we confirmed that alpha 2-3-linked sialic acids, and alpha 1-3(4)fucosylation are important for recognition. Similar results obtained with both types of immobilized targets for the three selectins indicated that the binding sites for sialic acid and sulfate are very close, or identical. While O-sulfate esters mostly improved L- and P-selectin recognition, effects depended upon their position and number. Furthermore, sulfation can also impart some "negative" specificity: the major capping group does not interact with E-selectin. The branched Core 2 sequence seemed to enhance L- and P-selectin binding, however, the best inhibitors still appeared to be sialyl Le(a) and 3'-sulfo-Le(x), with the aglycone group of the latter affecting binding. Of particular note, the "major capping group" of GlyCAM-1 was not an unusually potent nor highly selective inhibitor of L-selectin, even when studying the interaction of L-selectin with native GlyCAM-1 itself.

Carbohydrate Sequence↗
PubMed1997

Sialic acids as ligands in recognition phenomena.

The sialic acids are acidic monosaccharides typically found at the outermost ends of the sugar chains of animal glycoconjugates. They potentially can inhibit intermolecular and intercellular interactions by virtue of their negative charge. However, they can also act as critical components of ligands recognized by a variety of proteins of animal, plant, and microbial origin (sialic acid binding lectins). Recognition can be affected by specific structural variations and modifications of sialic acids, their linkage to the underlying sugar chain, the structure of these chains, and the nature of the glycoconjugate to which they are attached. Presented here is a summary of the various proteins that can recognize and bind to this family of monosaccharides, comparing and contrasting the structural requirements and mechanisms involved in binding. Particular attention is focused on the recently evolving information about sialic acid recognition by certain C-type lectins (the selectins), I-type lectins (e.g., CD22 and sialoadhesin), and a complement regulatory protein (the H protein). The last two instances are examples of the importance of the side chain of sialic acids and the effects of natural substitutions (e.g., 9-O-acetylation) of this part of the molecule.

Carbohydrate Sequence↗
PubMed1996

DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice.

Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.

Animals↗
PubMed1996

Regulation of sialic acid 9-O-acetylation during the growth and differentiation of murine erythroleukemia cells.

Sialic acids are typically found at the terminal position on vertebrate oligosaccharides. They are sometimes modified by an O-acetyl ester at the 9-position, potentially altering recognition of sialic acid by antibodies, lectins, and viruses. 9-O-Acetylation is known to be selectively expressed on gangliosides in melanoma cells and on N-linked chains in hepatocytes. Using a recently developed probe, we show here that in murine erythroleukemia cells, this modification is selectively expressed on another class of oligosaccharides, O-linked chains carried on cell surface sialomucins. These cells also express 9-O-acetylation on the ganglioside GD3, but this modification appears to be undetectable on the cell surface. Increasing cell density in culture is associated with a decrease in cell surface 9-O-acetylation of sialomucins. This change correlates with the spontaneous differentiation toward a mature erythroid phenotype. This down-regulation upon differentiation and entry into the G0/G1 stage of the cell cycle is confirmed by differentiation-inducing agents. In contrast, cells arrested in G2/M by the microtubule depolymerizing agent nocodazole show increased expression of cell surface 9-O-acetylated sialomucins (but not the 9-O-acetylated ganglioside). However, the microtubule stabilizer taxol does not induce this increase, showing that the nocodazole effect is independent of cell cycle stage. Indeed, direct analysis showed no correlation of 9-O-acetylation with cell cycle stage in rapidly growing cells, and shorter treatments with nocodazole also increased expression. Western blots of cell extracts confirmed that changes caused by differentiation and nocodazole are not due to redistribution of molecules from the cell surface. Indeed, following selective removal of 9-O-acetyl groups from the cell surface by a specific esterase, the recovery of expression is mediated by new synthesis rather than by redistribution from an internal pool. Thus, 9-O-acetylation on these sialomucins appears to be primarily regulated by the rate of synthesis, and the increase with nocodazole treatment is likely due to the inhibition of turnover of cell surface molecules. These data show that 9-O-acetylation of sialic acids in murine erythroleukemia cells is a highly regulated modification, being selectively expressed in a cell type-specific manner on certain classes of oligosaccharides and differentially regulated with regard to subcellular localization and to the state of cellular differentiation.

Acetylation↗
PubMed1996

Sialic acid 9-O-acetylation on murine erythroleukemia cells affects complement activation, binding to I-type lectins, and tissue homing.

O-Acetylation of the 9-hydroxyl group of sialic acids has been suggested to modify various recognition phenomena involving these molecules, but direct proof has been lacking in most situations. In the accompanying paper (Shi, W.-X., Chammas, R., and Varki, A. (1996) J. Biol. Chem. 261, 31517-31525), we report that the extent of 9-O-acetylation of cell surface sialic acids on murine erythroleukemia (MEL) cells can be modified by various manipulations, including differentiation, nocodazole treatment, and 9-O-acetyl esterase treatment. We have used this system to explore the putative roles of 9-O-acetylation in modulating alternative pathway complement activation, I-type lectin binding, and tissue homing. MEL cells are shown to be sensitive to lysis in vitro by the alternative pathway of human complement. Induced differentiation of the MEL cells causes resistance to lysis, and this correlates directly with extent of decrease in 9-O-acetylation. A similar resistance to alternative pathway lysis can be obtained by selective enzymatic removal of 9-O-acetyl groups from sialic acids. Conversely, the increase in cell surface 9-O-acetylation caused by nocodazole treatment correlates with increased sensitivity to alternative pathway lysis. Thus, a 9-O-acetyl group added to the side chain of cell surface sialic acids may abrogate its normal function in restricting alternative pathway activation. Indeed, the binding of human complement factor H, a negative regulator of the alternative pathway, is shown to be blocked by O-acetylation of the sialic acids on MEL cells. MEL cells are also shown to have cell surface ligands for the I-type lectins sialoadhesin and CD22. Sialoadhesin (but not CD22) binding is selectively enhanced by differentiation-induced loss of cell surface 9-O-acetylation and by direct enzymatic removal of the ester groups. Thus, some sialoadhesin ligands are masked by 9-O-acetylation, presumably because the side chain is required for recognition. Since sialoadhesin is expressed on some macrophages in vivo, we reasoned that tissue homing of MEL cells might be affected by O-acetylation. Indeed, enzymatic removal of cell surface 9-O-acetyl groups alters the tissue distribution of intravenously injected cells. In particular, de-O-acetylation caused significant increase in homing to the liver and spleen. These data demonstrate that cell surface 9-O-acetylation can affect a variety of biological recognition phenomena and provide a system for further exploration of the specific molecular mechanisms involved.

Acetylation↗
PubMed1996

Linkage-specific action of endogenous sialic acid O-acetyltransferase in Chinese hamster ovary cells.

9-O-Acetylation of sialic acids shows cell type-specific and developmentally regulated expression in various systems. In a given cell type, O-acetylation can also be specific to a particular type of glycoconjugate. It is assumed that this regulation is achieved by control of expression of specific 9-O-acetyltransferases. However, it has been difficult to test this hypothesis, as these enzymes have so far proven intractable to purification or molecular cloning. During a cloning attempt, we discovered that while polyoma T antigen-positive Chinese hamster ovary cells (CHO-Tag cells) do not normally express cell-surface 9-O-acetylation, they do so when transiently transfected with a cDNA encoding the lactosamine-specific alpha2-6-sialyltransferase (Galbeta1-4GlcNAc:alpha2-6-sialyltransferase (ST6Gal I); formerly ST6N). This phenomenon is reproducible by stable expression of ST6Gal I in parental CHO cells, but not upon transfection of the competing lactosamine-specific alpha2-3-sialyltransferase (Galbeta1-(3)4GlcNAc:alpha2-3-sialyltransferase; (ST6Gal III) formerly ST3N) into either cell type. Further analyses of stably transfected parental CHO-K1 cells indicated that expression of the ST6Gal I gene causes selective 9-O-acetylation of alpha2-6-linked sialic acid residues on N-linked oligosaccharides. In a similar manner, while the alpha2-3-linked sialic acid residue of the endogenous GM3 ganglioside of CHO cells is not O-acetylated, transfection of an alpha2-8-sialyltransferase (GM3:alpha2-8-sialyltransferase (ST8Sia I); formerly GD3 synthase) caused expression of 9-O-acetylation of the alpha2-8-linked sialic acid residues of newly synthesized GD3. These data indicate either that linkage-specific sialic acid O-acetyltransferase(s) are constitutively expressed in CHO cells or that expression of these enzymes is secondarily induced upon expression of certain sialyltransferases. The former explanation is supported by a low level of background 9-O-acetylation found in parental CHO-K1 cells and by the finding that O-acetylation is not induced when the ST6Gal I or ST8Sia I cDNAs are overexpressed in SV40 T antigen-expressing primate (COS) cells. Taken together, these results indicate that expression of sialic acid 9-O-acetylation can be regulated by the action of specific sialyltransferases that alter the predominant linkage of the terminal sialic acids found on specific classes of glycoconjugates.

Acetyltransferases↗