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)

The specific activities of UDP-galactose : GM2 galactosyltransferase and CMP-NAN : GM1 sialyltransferase were measured in total particulate fractions of individual hepatocellular carcinomas (hepatomas) and hepatic nodules, induced in the rat by a carcinogenic diet of 0.05% N-2-fluorenylacetamide alternating with a low protein basal diet. In all tumors except the smallest nodules, galactosyltransferase specific activities were increased compared to those of control livers from rats fed only basal diet. When relative specific activities were related to wet weight of nodules larger than 0.1 g were in two populations. Specific activities of nodules in one population overlapped those of poorly differentiated hepatomas whereas specific activities of the second population those of well differentiated hepatomas. Specific activities of the sialyltransferase were also increased above those in control livers but not with the same frequency or to the same extent as for the galactosyltransferase. As with galactosyltransferase, nodules were found in two major populations when specific activities were related to nodule wet weight. The data suggest that increased specific activities of galactosyltransferase and sialyltransferase in hepatic nodules may provide an early phenotypic indicator of diverging differentiation in hepatocarcinogenesis.
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PMID:Gangliosides of liver tumors induced by N-2 fluorenylacetamide III. Galactosyl and sialyl transferases in single carcinomas and nodules. 677 33

Golgi vesicles were isolated and purified from rat liver, in which the specific activities of glycosyltransferases (e.g. GM3:CMP-NeuAc sialyltransferase, GD3 synthase; GM3:UDP-GalNAc galactosaminyltransferase, GM2 synthase) were 50-60-times enriched relative to microsomes or total homogenate. Synthesis of gangliosides GM2 and GM1 in such Golgi vesicles is, in the absence of any detergents, stimulated 6-fold and 20-fold respectively by phosphatidylglycerol. Other phospholipids like phosphatidylethanolamine and phosphatidylserine are also significantly stimulatory. With 50 micrograms Golgi protein and 1 nmol UDP-GalNAc, optimal stimulation of GM2 synthase was obtained with 20 micrograms of phosphatidylglycerol and 7.5 nmol of the lipid acceptor GM3. Under the same experimental conditions this stimulation exceeds (by about 40%) that obtained with optimal amount (200 micrograms) of the detergent octylglucoside. Phosphatidylglycerol, on the other hand, has virtually no stimulatory activity on the synthesis of ganglioside GD3 either in the presence of Mg2+ or Mn2+, indicating that facilitation by phospholipid of GM3 transport into Golgi vesicles was not the basis of stimulation of GM2 synthesis. Tunicamycin inhibits the synthesis of gangliosides GM2 and GM1 in isolated Golgi vesicles, but only in the absence of detergents. In the presence of phosphatidylglycerol, GM2 synthesis, for example, was inhibited by 60% by 2 micrograms tunicamycin and more than 85% by 10 micrograms tunicamycin, per 50 micrograms Golgi membrane protein. The inhibition was stronger on GM1 synthesis: 85% with 2.5 micrograms of the antibiotic. The dependence on phosphatidylglycerol and the degree of inhibition by tunicamycin of the synthetic activities are strictly dependent on the intactness of the Golgi vesicles: both phenomena become increasingly less evident when the vesicles are pelleted, and frozen and thawed several times, and completely disappear when the vesicles are solubilized by detergents or disrupted by ultrasonication. Furthermore, tunicamycin inhibition is reversible by increased concentration of phosphatidylglycerol. All these results indicate that phosphatidylglycerol does not stimulate, and tunicamycin does not inhibit, the transferases themselves; rather, the two opposing effects might relate to carrier-mediated transport, e.g. of nucleotide sugars, across Golgi vesicles.
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PMID:Ganglioside biosynthesis in Golgi apparatus of rat liver. Stimulation by phosphatidylglycerol and inhibition by tunicamycin. 686 62

Total labeled glycolipids from thymocytes of leukemic AKR/J mouse thymus incubated for 24 h in the presence of the precursors [3H] galactose or [14C] glucosamine were found to exceed those from non-leukemic thymocytes. The amount of labeled compounds that co-migrated with monosialogangliosides (GM3 and GM2) and disialogangliosides (GD1a and GD1b) was higher, whereas incorporation into monosialoganglioside (GM1) and trisialoganglioside (GT1) was lower in leukemic than in non-leukemic thymocytes. Consistent with this altered pattern of ganglioside distribution was the finding of a higher activity of two of the sialyltransferase activities in homogenates of leukemic thymus as compared to normal thymus. About 2-fold higher activities of the enzymes CMP-AcNeu: lactosylceramide sialyltransferase and CMP-AcNeu: GM1 sialyltransferase were observed in leukemic thymus homogenate compared to homogenates of non-leukemic cells. The substrate affinity of sialyltransferase with GM1 as acceptor from the leukemic thymus was similar to that of the enzyme from normal thymus. Thus, our studies reveal an enzymatic basis for the enhanced rate of synthesis and altered ganglioside profile observed in malignant thymocytes, and are consistent with the general view on the pattern of acidic glycolipids in tumorigenesis.
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PMID:Glycolipid sialyltransferases in normal and neoplastic murine thymocytes. 731 48

The amount and type of sialylation of tumor cell membranes depends on the activity of a number of different sialyltransferase enzymes. For the detection of specific activities in human colorectal carcinoma tissue several glycoprotein and glycolipid acceptors were used: desialylated fetuin, alpha 1-acid glycoprotein, beta 2-glycoprotein I, ovine submaxillaris mucin, and the gangliosides GM1, GM2, GM3 and GD1a. Because of their possible relevance for metastasis, precursors of Le(a) and Le(x) antigens, too, were employed, namely neoglycolipids produced by coupling LcOse4 or NeoLcOse4 oligosaccharides to L-alpha-phosphatidyl-ethanol-amine-dipalmitoyl. Our data indicate that human colorectal tumor tissue contains two highly active sialyltransferase enzymes, which are only weakly expressed in normal mucosa. These are a N-glycan-specific alpha 2,6-sialyltransferase, which was significantly increased in metastasizing tumors, and a Gal beta 1,3Gal-NAc-specific sialyltransferase, which was increased in tumors of early stages. A shift to enhanced alpha 2,6-sialylation of membrane glycoproteins during carcinogenesis was demonstrated by lectin ELISA analysis of magneto-bead separated tumor cells. Quantitative determination of specific sialyltransferase activities may be a sensitive tool for detection and monitoring of colon carcinoma.
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PMID:Different sialyltransferase activities in human colorectal carcinoma cells from surgical specimens detected by specific glycoprotein and glycolipid acceptors. 819

Addition of sialic acid residues in the human pathogen Trypanosoma cruzi glycoconjugates is mediated by a trans-sialidase and not by a CMP-sialic acid:glycoconjugate sialyltransferase. Incubation of trans-sialidase with N-[galactose-14C]acetyllactosamine and O-linked oligosaccharides, N-linked glycopeptides (both obtained from fetuin) or sialyllactose showed that the last three compounds were donors of sialic acid residues to the first one. Moreover, N- and O-linked oligosaccharides in asialofetuin and asialomucin, respectively, served as acceptors of sialic acid units. Gangliosides GM3, GD1a and GT1b but not GM2, GM1a nor GD1b donated sialic acid units to N-acetyllactos amine when incubated with trans-sialidase. This showed that only sialic acid units bound to terminal galactosyl residues were transferred. GM1a was converted to GD1a, and GD1b to GT1b when incubated with the appropriate donor. The fact that asialo-GM1a was converted to a ganglioside migrating as GD1a on thin-layer chromatography suggested that sialic acid units may be transferred to internal galactosyl residues, although once linked to those residues they can not be further transferred to other glycoconjugates. Sialic acid residues linked alpha 2,3- but not alpha 2,6- or alpha 2,8- were transferred by the trans-sialidase. Methyl beta-galactoside but not methyl alpha-galactoside served as acceptor of sialic acid units, thus suggesting that terminal alpha-linked galactosyl units in T. cruzi and mammalian glycoproteins are not sialylated by the enzyme. As the trans-sialidase employed in these experiments has been shown to be located on the external surface of the parasite and to be shed to the medium, the relatively broad specificity shown by the enzyme with respect to protein- and lipid-linked oligosaccharides strongly suggests that infection by T. cruzi might alter the sialic acid distribution in glycoproteins and glycolipids of the mammalian host.
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PMID:The action of Trypanosoma cruzi trans-sialidase on glycolipids and glycoproteins. 847 49

A human Gal beta(1-3/1-4)GlcNAc alpha 2,3-sialyltransferase, called ST-4, is a sialyltransferase involved in the in vivo biosynthesis of sialyl Lewis X (NeuNAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc) determinant. The ST-4 enzyme could utilize nLc4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 2 sugar chain, Lc4Cer (Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer) containing type 1 sugar chain, Gg4Cer (Gal beta 1-3GalNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer), and LacCer as glycolipid acceptor substrates, but not other neutral glycolipids (GalCer, GlcCer, Gb3Cer, Gg3Cer, Gb4Cer) and gangliosides (GM1a, GM2, GM3, GD1a, GD1b, and GT1b) as substrates. The order of sialic acid incorporation into glycolipids for the enzyme was nLc4Cer > Gg4Cer > Lc4Cer > LacCer. The apparent Km values of ST-4 for nLc4Cer and Gg4Cer were 0.47 and 2.5 mM, respectively. Thus, the ST-4 could efficiently utilize both nLc4Cer and Gg4Cer as glycolipid acceptor substrates in vitro, suggesting that the substrate specificity of the enzyme may be similar to that of a glycolipid sialyltransferase (SAT-3), which is defined as the enzyme that uses both nLc4Cer and Gg4Cer as glycolipid acceptor substrates.
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PMID:Glycolipid acceptor specificity of a human Gal beta(1-3/1-4) GlcNAc alpha 2,3-sialyltransferase. 855 8

Many Golgi glycosyltransferases are type II membrane proteins which are cleaved to produce soluble forms that are released from cells. Cho and Cummings recently reported that a soluble form of alpha1, 3-galactosyltransferase was comparable to its membrane bound counterpart in its ability to galactosylate newly synthesized glycoproteins (Cho,S.K. and Cummings,R.D. (1997) J. Biol. Chem., 272, 13622-13628). To test the generality of their findings, we compared the activities of the full length and soluble forms of two such glycosyltransferases, ss1,4 N-Acetylgalactosaminyltransferase (GM2/GD2/ GA2 synthase; GalNAcT) and beta galactoside alpha2,6 sialyltransferase (alpha2,6-ST; ST6Gal I), for production of their glycoconjugate products in vivo . Unlike the full length form of GalNAcT which produced ganglioside GM2 in transfected cells, soluble GalNAcT did not produce detectable GM2 in vivo even though it possessed in vitro GalNAcT activity comparable to that of full length GalNAcT. When compared with cells expressing full length alpha2,6-ST, cells expressing a soluble form of alpha2,6-ST contained 3-fold higher alpha2,6-ST mRNA levels and secreted 7-fold greater alpha2,6-ST activity as measured in vitro , but in striking contrast contained 2- to 4-fold less of the alpha2,6-linked sialic acid moiety in cellular glycoproteins in vivo . In summary these results suggest that unlike alpha1,3-galactosyltransferase the soluble forms of these two glycosyltransferases are less efficient at glycosylation of membrane proteins and lipids in vivo than their membrane bound counterparts.
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PMID:Two soluble glycosyltransferases glycosylate less efficiently in vivo than their membrane bound counterparts. 963 44

The effect of changing the ganglioside composition of Chinese hamster ovary K1 cells on the function of the epidermal growth factor receptor (EGFr) was examined by studying the signalling pathway generated after the binding of epidermal growth factor (EGF) both in cells depleted of glycosphingolipids by inhibiting glucosylceramide synthase activity and in cell lines expressing different gangliosides as the result of stable transfection of appropriate ganglioside glycosyltransferases. After stimulation with EGF, cells depleted of glycolipids showed EGFr phosphorylation and extracellular signal-regulated protein kinase 2 (ERK2) activity as parental cells expressing GM3 [ganglioside nomenclature follows Svennerholm (1963) J. Neurochem. 10, 613-623] or as transfected cells expressing mostly GM2 and GD1a as the result of stable transfection of UDP-GalNAc:LacCer/GM3/GD3 N-acetylgalactosaminyltransferase. However, cells stably transfected with CMP-NeuAc:GM3 sialyltransferase and expressing GD3 at the cell surface showed both decreased EGFr phosphorylation and ERK2 activation after stimulation with EGF. Results suggest that changes in the ganglioside composition of cell membranes might be important in the regulation of the EGF signal transduction.
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PMID:Modulation of epidermal growth factor receptor phosphorylation by endogenously expressed gangliosides. 1128 35

Gangliosides such as GD3, GM2, and GD2 are abundantly expressed on the cell surfaces of various malignant cells, suggesting the potential for anti-ganglioside antibody therapy for tumors. Anti-ganglioside GD2 antibody treatment is currently undergoing clinical trials for melanoma and neuroblastoma. We previously reported high in vivo antitumor effects of anti-GM2 ganglioside antibody against lung cancer. To determine whether anti-GM2 antibody may be clinically indicated for gastrointestinal cancers, we evaluated the mRNA expression of alpha2,8 sialyltransferase, a GD3 synthase, and beta1,4 N-acetylgalactosaminyltransferase (beta1,4 GalNAc-T), a GM2/GD2 synthase, in gastrointestinal cancers. We performed modified semi-quantitative RT-PCR, which reduces complexity incidental to radiolabeling on samples taken from small surgically removed clinical specimens. Stomach (19/22) and colorectal (21/30) cancers showed decreased expression of alpha2,8 sialyltransferase as compared with respective normal tissues (P < 0.05). In contrast, increased expression of beta1,4 GalNAc-T was detected in both types of tumors. Clinicopathological analysis revealed significantly higher expression level of alpha2,8 sialyltransferase in the poorly differentiated than in the well-differentiated stomach cancer group (P < 0.05). Furthermore, the expression level of alpha2,8 sialyltransferase was significantly decreased in male as compared with female colorectal cancer patients (P < 0.05). These results suggest that expression level of GM2 ganglioside is elevated in gastrointestinal cancer, and that anti-GM2 antibody may be applicable to its treatment.
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PMID:Decreased expression of alpha2,8 sialyltransferase and increased expression of beta1,4 N-acetylgalactosaminyltransferase in gastrointestinal cancers. 1185 18

We have synthesized several ganglio-oligosaccharide structures using glycosyltransferases from Campylobacter jejuni. The enzymes, alpha-(2-->3/8)-sialyltransferase (Cst-II), beta-(1-->4)-N-acetylgalactosaminyltransferase (CgtA), and beta-(1-->3)-galactosyltransferase (CgtB), were produced in large-scale fermentation from Escherichia coli and further characterized based on their acceptor specificities. 2-Azidoethyl-glycosides corresponding to the oligosaccharides of GD3 (alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-), GT3 (alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp-), GM2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), GD2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), GT2 (beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->8)-alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-), and GM1 (beta-D-Galp-(1-->3)-beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-) were synthesized in high yields (gram-scale). In addition, a mammalian alpha-(2-->3)-sialyltransferase (ST3Gal I) was used to sialylate GM1 and generate GD1a (alpha-D-Neup5Ac-(2-->3)-beta-D-Galp-(1-->3)-beta-D-GalpNAc-(1-->4)-[alpha-D-Neup5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-) oligosaccharide. We also cloned and expressed a rat UDP-N-acetylglucosamine-4'epimerase (GalNAcE) in E. coli AD202 cells for cost saving in situ conversion of less expensive UDP-GlcNAc to UDP-GalNAc.
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PMID:Chemoenzymatic synthesis of 2-azidoethyl-ganglio-oligosaccharides GD3, GT3, GM2, GD2, GT2, GM1, and GD1a. 1600 59


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