Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.7 (sialyltransferase)
1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many previous studies have implicated cell surface saccharides, and sialylglycoconjugates in particular, as important mediators of tumor cell metastasis. In this report, we have used three different specific sialidases and a highly sensitive high-performance liquid chromatographic sialic acid assay to probe the cell surfaces of several murine adrenal carcinoma variants. In contrast to several earlier studies on other metastatic variants, we find no significant differences in the overall levels of cell surface or total cellular sialic acid among three Y1 murine adrenal carcinoma variants with widely different metastatic phenotypes. However, using highly purified, linkage-specific sialyltransferases, in conjunction with V. cholerae sialidase, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we do find striking differences in oligosaccharide structures underlying the sialic acid moieties. Two tumorigenic and metastatic variants (F2 and F4) contain about 6-fold more penultimate Gal beta 1----4GlcNAc sialylation sites than a related tumorigenic but nonmetastatic variant (HSR) when CMP-[3H]-N-acetylneuraminic acid and the Gal beta 1----4GlcNAc alpha 2,6 sialyltransferase are used to probe the adrenal carcinoma cell surfaces. The metastatic variants also are found to contain 4- to 4.5-fold more Gal beta 1----3GalNAc sialylation sites than the nonmetastatic variant when the Gal beta 1----3GalNAc alpha 2,3 sialyltransferase is used as a cell surface probe. Earlier work, which used the same sialyltransferase probes on sialidase-treated murine melanoma variants (A. Passaniti and G. W. Hart, J. Biol. Chem., 263: 7591-7603, 1988), also showed similar quantitative differences in penultimate structures between metastatic variants. However, in contrast to the adrenal carcinoma cells, the highly metastatic melanoma cells have severalfold lower levels of sialylatable penultimate Gal beta 1----4GlcNAc and Gal beta 1----3GalNAc saccharides compared to their nonmetastatic counterparts. Thus, while the precise structural alterations or surface accessibilities of penultimate saccharides appear to be cell type dependent, these results suggest that pronounced changes in penultimate cell surface sialo-oligosaccharide moieties occur during progression to a malignant phenotype in two widely different tumor systems. These types of alterations in the underlying penultimate oligosaccharide structures of cell surface sialoglycoconjugates may be a common feature of highly metastatic cells arising from very different tumor cell types.
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PMID:Adrenal carcinoma tumor progression and penultimate cell surface oligosaccharides. 155 26

Human chorionic gonadotrophin (hCG) is a heterodimeric glycoprotein hormone consisting of an alpha- and a beta-subunit, both containing two N-linked, complex-type glycans. Using this hormone as a model glycoprotein, the influence of its polypeptide part on the activity and specificity of bovine colostrum CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase (alpha 6-sialyltransferase) was investigated. Initial rates of sialic acid incorporation into the desialylated glycans of hCG alpha and hCG beta in the heterodimer were higher with the alpha-subunit. This appeared to be due to a higher V which, together with a slightly lowered affinity (higher Km), resulted in a higher kinetic efficiency of the sialyltransferase for the glycans of this subunit. By contrast, the kinetic parameters did not differ significantly when the subunits were in the free form, indicating that the differences in the kinetics of sialylation found for the subunits in the heterodimeric state were not caused by the differences in N-linked carbohydrate structures of the subunits. It is proposed that these effects are due to conformational constraints which the polypeptide moieties put on the glycan chains upon dimerization. Furthermore, it was investigated whether the polypeptide of hCG would interfere with the sialyltransferase so as to alter the branch specificity of the enzyme. 1H-NMR spectroscopy (400 MHz) of the glycan chains, alpha 6-sialylated in vitro, showed that the enzyme highly prefers the galactosyl residue at the Gal beta 1----4GlcNAc beta 1----2-Man alpha 1----3Man branch for attachment of the first mol of sialic acid into the diantennary glycans of desialylated hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The polypeptide part of human chorionic gonadotrophin affects the kinetics of alpha 6-sialylation of its N-linked glycans but does not alter the branch specificity of CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase. 160 56

The activity of four different sialyltransferases acting on N- or O-linked chains of glycoproteins was studied in brains of 19 days-old embryos, 1-day-old newborns and adult rats. By using asialofetuin, fetuin and N-acetyllactosamine as acceptors, it has been possible to measure independently the following enzyme activities: CMP-NeuAc:Gal beta 1-3GalNAc alpha(2-3)-sialyltransferase (EC 2.4.99.4), CMP-NeuAc:Gal beta 1-4GlcNAc alpha(2-3)-sialyltransferase (EC 2.4.99.6), CMP-NeuAc:Gal beta 1-4GlcNAc alpha(2-6)-sialyltransferase (EC 2.4.99.1) and CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-3GalNAc alpha(2-6)-sialyltransferase (EC 2.4.99.7). The specific activity of the first three enzymes which act on asialylated acceptors showed a 2.6-fold decrease in a parallel manner after ontogenic development, while the activity of NeuAc alpha 2-3Gal beta 1-3GalNAc alpha(2-6)-sialyltransferase was four times lower in adult than in embryonic brain, showing a stronger dependence on ontogenic development. Despite the higher level of sialyltransferases able to act on glycoproteins, in fetal brain these glycoproteins do not contain a higher amount of sialic acid.
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PMID:Sialyltransferases of developing rat brain. 172 33

A Gal beta 1-4GlcNAc alpha (2-6)-sialyltransferase from human liver was purified 34,340-fold with 18% yield by dye chromatography on Cibacron Blue F3GA and cation exchange FPLC. The enzyme preparation was free of other sialyltransferases. It did not contain CMP-NeuAc hydrolase, protease, or sialidase activity, and was stable at -20 degrees C for at least eight months. The donor substrate specificity was examined with CMP-NeuAc analogues modified at C-5 or C-9 of the N-acetylneuraminic acid moiety. Affinity of the human enzyme for parent CMP-NeuAc and each CMP-NeuAc analogue was substantially higher than the corresponding Gal beta 1-4GlcNAc alpha (2-6)-sialyltransferase from rat liver.
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PMID:Purification and characterization of alpha (2-6)-sialyltransferase from human liver. 182 12

We have studied the Gal beta 1-3GalNAc-R alpha 2,3 sialyltransferase from C6 glioma cells transferring Neu5Ac from CMP-Neu5Ac onto O-glycans of glycoproteins. Using synchronized C6 glioma cells, we showed that the alpha 2,3 sialyltransferase activity was inhibited by tunicamycin to a greater extend than DNA and protein biosynthesis suggesting inhibition of N-glycosylation of this enzyme. Additional demonstration of N-glycosylation of the alpha 2,3 sialytransferase was provided through ConA-Sepharose binding. Treatment of partially purified alpha 2,3 sialytransferase by peptide-N-glycosidase F showed a significative inhibition demonstrating that N-glycan moiety is required for complete activity of the C6 glioma cell alpha 2,3 sialyltransferase.
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PMID:Study of O-glycan sialylation in C6 cultured glioma cells: evidence for post-translational regulation of a beta-galactoside alpha 2,3 sialyltransferase activity by N-glycosylation. 187 58

The acceptor specificities of four sialytransferases (I, II, IV and V) involved in ganglioside biosynthesis were studied in Golgi vesicles derived from rat liver. The activities of these sialytransferases were strongly detergent-dependent. Competition experiments with different detergent concentrations using LacCer (Gal beta 1----4Glc beta 1----1Cer), GM1a [Gal beta 1----3GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1Cer] and GD1b [Gal beta 1----3GalNAc beta 1----4(NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1Cer] as substrates, and as mutual inhibitors for ganglioside sialyltransferase activity, suggested that sialyltransferase IV was able to catalyze the sialyltransfer in alpha 2----3 linkage to the galactose residues of LacCer as well as of GM1a and GD1b. The other three sialyltransferases (I, II and V) seemed to be quite specific for their respective glycolipid acceptors, LacCer, GM3 and GM1b, GD1a and GT1b. Furthermore the kinetic data showed that sialyltransferase I was inactive at higher detergent concentrations (greater than 75 micrograms Triton CF-54); under these conditions, formation of GM3 and GD1a was catalyzed only by sialyltransferase IV. These results have been integrated into a model for ganglioside biosynthesis and its regulation.
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PMID:Substrate specificity of alpha 2----3-sialyltransferases in ganglioside biosynthesis of rat liver golgi. 199 63

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immunodeficiency affecting B lymphocytes, T lymphocytes, and platelets. Previous studies on lymphocytes from WAS patients have revealed that leu-kosialin (CD43), a cell-surface glycoprotein bearing approximately 90 O-linked oligosaccharide chains, shows an aberrant electrophoretic mobility. To determine whether this finding reflects a different pattern of O-linked glycosylation in WAS cells, we have compared healthy individuals and WAS patients with respect to glycosyltransferase activities in T lymphocytes, platelets, and Epstein-Barr virus (EBV)-immortalized B cell lines. Stimulation of peripheral T cells from normal individuals in vitro with anti-CD3 antibodies and interleukin-2 was associated with a 3-fold increase in UDP-GlcNAc:Gal beta 3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (core 2 GlcNAc-T) from 0.8 to 2.2 nmol/mg/h. In contrast, peripheral T lymphocytes from WAS patients showed an inversion of this phenotype with high core 2 GlcNAc-T activity in unstimulated cells (2.3 nmol/mg/h) and a 2-3-fold decrease in activity following stimulation. Core 2 GlcNAc-T activity was also three times higher in platelets from WAS patients than in normal platelets. Glycosyltransferase activities were measured in immortalized B cell lines established from WAS and normal subjects by infection with EBV. Core 2 GlcNAc-T was less than 0.4 nmol/mg/h in WAS EBV-B cell lines compared to 2.4 nmol/mg/h in EBV-B cell lines from healthy individuals, In contrast, CMP-SA:SA alpha 2-3Gal beta 1-3GalNAc-R (where SA represents sialyl (sialic acid to GalNAc) alpha 6-sialyltransferase II activity was 2.0 nmol/mg/h in the WAS EBV-B cell and less than .01 nmol/mg/h in EBV-B cell lines derived from normal subjects. Eleven other glycosyltransferase activities were measured and found to be similar in EBV-B cell lines from WAS and normal individuals. Polylactosamine sequences were much reduced in the O-linked oligosaccharides of CD43 from WAS EBV-B cells consistent with decreased core 2 GlcNAc-T activity and expression of core 1 oligosaccharides in the cells. In conclusion, B cells, T cells, and platelets in WAS patients show abnormal expression of two developmentally regulated glycosyltransferases, consistent with the idea that the WAS immunodeficiency is due to a failure of normal lymphocyte maturation.
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PMID:Aberrant O-linked oligosaccharide biosynthesis in lymphocytes and platelets from patients with the Wiskott-Aldrich syndrome. 200 80

The CA 125 antigenic determinant has been shown to be elevated in the serum of ovarian cancer patients and is a useful prognostic marker. The chemical epitope which characterizes the CA 125 antigen is found on a high molecular weight glycoprotein and has been suggested to be carbohydrate in nature. This study was undertaken to establish the relationship of a carbohydrate to the epitope recognized by the monoclonal antibody, OC 125. Along this line a carbohydrate structure conjugated to bovine serum albumin (BSA), was enzymatically sialylated using a purified sialyltransferase to yield NeuAcGal[GlcNAc]GalNAc-OC6H4N = N-BSA. This sialylated product was used to immunize a goat and two rabbits for the development of polyclonal antisera. The resultant antisera were tested against related carbohydrates in EIA biased competitive inhibition assays. It was determined that the GlcNAc(beta 1-6)GalNAc residue was immunologically dominant for all antisera tested. As the immune response matured (greater than 40 days), there was an increase in the proportion of the antibodies that were directed to the NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc residue compared to the nonsialylated form. Known CA 125 molecules did not inhibit the binding of raised antisera to the sialylated product, nor did the sialylated product react with OC 125 monoclonal antibodies. It was therefore concluded that the carbohydrate structure in question is not the epitope, or is not a large enough part of the epitope to be recognized in these assays by the OC 125 monoclonal antibodies.
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PMID:Antigenic studies on an enzymatically sialylated carbohydrate: NeuAc(alpha 2-3)Gal(beta 1-3)[GlcNAc(beta 1-6)]GalNAc. 205 2

1. Rat Gal beta 1-4GlcNAc alpha 2-6sialyltransferase (E.C. 2.4.99.1) is released from Golgi membranes by cleavage of a portion of the enzyme containing the active site from a membrane anchor; this effect was most dramatic during the acute phase response. The enzyme that cleaved sialyltransferase had the properties of cathepsin D was most active at pH 5.6 and was likely of lysosomal origin (Lammers and Jamieson, 1988). 2. The acute phase response of sialyltransferase in mouse and guinea pig was previously found to differ from that in the rat. Release of sialyltransferase from mouse and guinea pig Golgi membranes has now been studied in order to make a comparison with the rat system. 3. Maximum release of sialyltransferase from mouse and guinea pig Golgi occurred at pH 4.6 and 5.2, respectively; like the rat a cathepsin D-like proteinase was responsible for release of both enzymes. 4. Immunoblot analysis showed that membrane-bound rat and mouse sialyltransferase had Mr 49,000, whereas the guinea pig enzyme had Mr 42,000. The released form of the rat enzyme had Mr 42,000, but released forms of mouse and guinea pig enzymes had Mr 38,000 suggesting a different cleavage site for these two enzymes compared to the rat enzyme.
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PMID:Cathepsin D-like activity in the release of Gal beta 1-4GlcNAc alpha 2-6sialyltransferase from mouse and guinea pig liver Golgi membranes during the acute phase response. 210 70

beta 1,4-N-Acetylgalactosaminyltransferase (beta 1,4GalNAc-transferase) and alpha 2,3-sialyltransferase are both involved in the biosynthesis of the Sda blood group antigen, which is also present in cells of large intestine. The expression of these enzymes and of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine was investigated in rat intestinal cells and correlated with both cell differentiation and extent of postnatal maturation. The beta 1,4GalNAc-transferase activity was exclusively found in epithelial cells of the large intestine, preferentially in the proximal segments suggesting a proximal-distal gradient of expression. The beta 1,4GalNAc-transferase and alpha 2,3-sialyltransferase activity towards N-acetyl-lactosamine were expressed in all cell fractions of the colonic crypt, with a maximum activity in the deeply located cells; therefore Sda antigen biosynthesis appears to occur preferentially at a specific stage of cell differentiation. By using N-acetyl-lactosamine as an acceptor, the predominant sialyltransferase in the colon cells was that capable of adding sialic acid in the alpha 2,3- linkage, whereas in the ileum cells the major enzyme was that forming the alpha 2,6-isomer. There were dramatic changes in the expression of colonic beta 1,4GalNac-transferase and of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine during postnatal maturation. The former enzyme, practically absent at birth, increased slowly in the first days of life and then rapidly after weaning; by contrast, the latter enzyme was largely expressed only in newborn animals. As the colonic alpha 2,3-sialyltransferase activity towards N-acetyl-lactosamine did not change during the postnatal period, the ratio between the alpha 2,6- and alpha 2,3-sialyltransferase activities was reversed after weaning.
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PMID:Postnatal development of rat colon epithelial cells is associated with changes in the expression of the beta 1,4-N-acetylgalactosaminyltransferase involved in the synthesis of Sda antigen of alpha 2,6-sialyltransferase activity towards N-acetyl-lactosamine. 211 76


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