The P-galactoside a-2,6-sialyltransferase activity of Fisher rat fibroblasts is enhanced by dexamethasone while the activity of the P-galactoside a-2,3-sialyltransferase remains unchanged. This glucocorticoid-dependent activation can be inhibited by the antagonist RU 38.486 and results from an elevated transcription rate of the 4.7-kb mRNA previously characterized in rat fibroblasts, distinct from the 4.3-kb liver-restricted mRNA. As shown by the binding of radiolabelled Sambucus nigra agglutinin, this activation leads to an increase of NeuNAc(a2-6)Gal sequences on glycoproteins isolated from the dexamethasone-treated cells.It is now well documented that the glycan moieties of glycoconjugates play an important part in the biological roles of these molecules, for instance in recognition phenomena such as protein targetting [l] or cell-cell interactions [2,3] and that N-acetylneuraminic acid (sialic acid) residues are involved in adhesion, mobility and recognition of cells [4-61. In particular, some adhesion molecules specifically recognize sialoglycoconjugates [7 -91 and the role of lectin/glycan interactions in the early stage of monocyte/endothelial-cell interactions has been clearly demonstrated during inflammation [5].The structures of the glycans are greatly diversified and often specific for tissues, species or cells [lo] and may be modified according to physiological [ll] or pathological states [12, 131. For example, malignant cells express a larger amount of multiantennary and more sialylated N-linked glycans than do their normal counterparts [14, 151. Since the oligosaccharide chains are synthezised in the Golgi apparatus by specific glycosyltransferases, the appearance of a certain glycan requires the expression of these glycosyltransferases. These could be modulated by intracellular and/or extracellular signals.Glucocorticoids interact via the glucocorticoid-receptor pathway with a large number of cells including fibroblastic cells [16] and the binding of the hormone/receptor complex to specific DNA-response elements leads to an enhancement or an inhibition of the transcription of some related genes. Dur- Abbreviations. a-2,3-sialyltransferase, CMP-N-acetylneuraminate-Gal(B 1-3/4)GlcNAc a-2,3-sialyltransferase; a-2,6-sialyltransferase, CMP-N-acetylneuraminate-Gal(/3l-4)GlcNAc cr-2,6-sialyltransferase; FR3T3, Fisher rat fibroblast; GRE, glucocorticoid-response element.Enzymes. CMP-N-acetylneuraminate-Gal@ 1 -4)GlcNAc a-2,6-sialyltransferase (EC 2.4.99.1); CMP-N-acetylneuraminate-Gal@ 1-3/4)GlcN Ac a-2,3-sialyltransferase (EC 2.4.99.6).ing the acute-phase response of the liver to tissue injury, an elevation of sialyltransferase activity has been observed in the liver and serum [17]. The P-galactoside a-2,6-sialyltransferase (a-2,6-sialyltransferase) transfers sialic acid residues from CMP-NeuNAc onto non-reducing terminal N-acetyllactosamine sequences of N-linked glycans [18] and recent reports have shown that the dexamethasone-induced increase of this activity in the liver [19] results from an ele...

No abstract

We have investigated the activity of CMP-Neu5Ac:Gal beta 1-3GalNAc alpha-2,3-sialyltransferase (EC 2.4.99.4) in FR3T3 cells transformed by the Ha-ras oncogene in which we have previously demonstrated the higher expression of the beta-galactosidase alpha-2,6-sialyltransferase (EC 2.4.99.1) [21]. We demonstrate that the presence of the activated ras gene decreases the activity of this specific alpha-2,3-sialyltransferase fourfold. According to the kinetic parameters and to mixing experiments, we can assume that this decreased enzymatic activity reflects a decrease in the number of active O-glycan alpha-2,3-sialyltransferase polypeptides in ras-transformed cells. However, no change in the binding of Peanut agglutinin was observed on the cell surface of ras-transformed FR3T3 suggesting that no change in the sialylation of O-glycan core 1 appeared in these cells, although the activity of the alpha-2,3-sialyltransferase was decreased.

No abstract