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)

Rat liver beta-galactoside alpha-2,6-sialyltransferase and Vibrio cholerae sialidase were used with cytidine-5'-monophospho-N-acetyl-[3H]neuraminic acid (CMP-[3H]NeuAc) to specifically probe the distribution and sialylation state of Gal beta 1-4GlcNAc residues on N-linked saccharides on the surfaces of murine lymphocytes. The relative extent of exogenous sialyltransferase-mediated sialylation (per cellular protein) was thymocytes greater than T-cells greater than T-cell lymphoma (EL-4) greater than B-cells greater than B-cell lymphoma (AKTB-1b) greater than splenocytes. Prior desialylation increased exogenous resialylation by 23.8-, 13.1-, 7.1-, 7.9-, 7.0-, and 5.3-fold for splenocytes, B-cells, T-cells, EL-4, AKTB-1b, and thymocytes, respectively. Though numerous glycoproteins were labeled, the majority of the Gal beta 1-4GlcNAc residues were detected on a relatively small number of cell surface proteins, many of which are well-defined lymphocyte antigens. Gal beta 1-4GlcNAc residues on thymocytes were found to exist in an undersialylated state on T200 but not on other antigens (e.g., Thy-1). T200 was found to be fully sialylated on mature cells (i.e., hydrocortisone-resistant thymocytes and splenic T-cells), suggesting that its sialylation state is developmentally regulated. These studies indicate that the number, sialylation state, and polypeptide distribution of the penultimate structure, Gal beta 1-4GlcNAc, differ on N-linked saccharides on the surfaces of different lymphocyte populations.
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PMID:Surfaces of murine lymphocyte subsets differ in sialylation states and antigen distribution of a major N-linked penultimate saccharide structure. 213 33

1. Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase was assayed in FAZA hepatoma cells and the cell culture medium following growth of cells in presence of dexamethasone and phorbol ester. 2. There was about a seven-fold increase in sialyltransferase activities in cells and medium in presence of dexamethasone with the maximum effect occurring at 10(-6)-10(-7) M dexamethasone. 3. The presence of 10(-6) M phorbol ester in the culture medium increased sialyltransferase activities in cells and medium by ca 40% over the values found with dexamethasone alone. 4. The use of the FAZA hepatoma cell line for studies on sialyltransferase is compared with the primary hepatocyte system reported on earlier (Woloski et al., 1986).
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PMID:Stimulation of release of Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase from the FAZA hepatoma cell line by dexamethasone and phorbol ester. 218 55

Little is currently known about the mechanisms by which the cellular glycosylation machinery is regulated to produce cell type-specific glycosylation sequences on glycoprotein and glycolipid sugar chains. Previously, we have shown that one enzyme involved in terminal glycosylation, beta-galactoside alpha 2,6-sialyltransferase, is expressed in a tissue-specific fashion, with the highest enzyme activity as well as mRNA levels being found in the liver. In addition, the liver mRNA was found to be 4.3 kilobases (kb) in size as compared to a larger message of 4.7 kb in other tissues. To understand the cellular regulation of expression of this sialyltransferase, we have cloned the rat gene encoding the 4.3-kb liver mRNA and found that it spans 40 kb of genomic DNA and contains 6 exons. The gene was found to be very similar in size and exon organization to the murine beta 1,4-galactosyltransferase gene, even though this enzyme has no sequence homology to alpha 2,6-sialyltransferase. The promoter responsible for the production of the liver alpha 2,6-sialyltransferase mRNA is approximately 50-fold more active in a hepatoma cell line known to express this enzyme (HepG2) than in a cell line shown not to express this enzyme (Chinese hamster ovary) and contains consensus binding sites for the liver restricted transcription factors HNF-1 and DBP as well as the transcription factors AP-1 and AP-2. These observations are in accord with the restricted expression of the 4.3-kb mRNA, and provides evidence for the cellular regulation of glycosylation at the level of transcription.
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PMID:Organization of the beta-galactoside alpha 2,6-sialyltransferase gene. Evidence for the transcriptional regulation of terminal glycosylation. 224 92

We have examined the role of CMP-NeuAc:Gal beta 1-3GalNAc-R alpha(2-3)-sialyltransferase in fresh leukemia cells and leukemia-derived cell lines. Enzyme activity in normal granulocytes using Gal beta 1-3GalNAc alpha-o-nitrophenyl as substrate was 1.5 +/- 0.7 nmol/mg/h whereas activity in morphologically mature granulocytes from 6 patients with chronic myelogenous leukemia (CML) was 4.2 +/- 1.6 nmol/mg/h (P less than 0.05). Myeloblasts from 5 patients with CML in blast crisis showed enzyme activity levels of 6.5 +/- 2.5 nmol/mg/h. From 2 patients with CML, both blasts and granulocytes were obtained, with higher enzyme activity in the patients' blasts (7.1 nmol/mg/h) than in their granulocytes (4.9 nmol/mg/h) in both cases, suggesting that the increase in enzyme activity is related to the differentiation or proliferation status of the CML cells. However, similarly high enzyme levels were also seen in myeloblasts from acute myeloblastic leukemia patients (5.6 +/- 1.4 nmol/mg/h) and in some acute myeloblastic leukemia-derived cell lines (KG1a and HL60), suggesting that increased levels of this enzyme are not directly correlated with the presence of the Ph1 chromosome. This alpha(2-3)-sialyltransferase activity can also be detected in normal peripheral blood lymphocytes and exhibits increased activity in chronic lymphocytic leukemia cells and acute lymphoblastic leukemia. These data suggest that the level of enzyme activity may vary with growth rate and maturation status in myeloid and lymphoid hemopoietic cells. Finally, we have identified a glycoprotein in acute myeloblastic leukemia cells that serves as a substrate for the alpha(2-3)-sialyltransferase. The desialylated form of the glycoprotein was resialylated in vitro by the purified placental form of this alpha(2-3)-sialyltransferase and exhibits a molecular weight of about 150,000.
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PMID:Human leukemic myeloblasts and myeloblastoid cells contain the enzyme cytidine 5'-monophosphate-N-acetylneuraminic acid:Gal beta 1-3GalNAc alpha (2-3)-sialyltransferase. 237 65

Granulocytes from patients with chronic myelogenous leukemia (CML) are morphologically identical to their normal counterparts but show marked differences in circulation patterns and in some membrane properties. We have previously shown that there is abnormal lectin binding to CML granulocytes, and aberrant sialylation of membrane glycoproteins. To examine the changes in sialylation of CML granulocytes further, we have studied membrane preparations from CML and normal granulocytes for specific sialyltransferase activity. Because sialyltransferase enzymes are specific for the configuration of the acceptor group, enzyme activity was assayed by measuring transfer of sialic acid from CMP-14C-sialic acid to substrates of defined structure. As compared with those of normal counterparts, CML extracts catalyzed a 50% higher overall rate of sialylation of asialofetuin, a substrate possessing both N- and O-linked acceptors. Studies of enzyme specificity utilizing porcine and ovine submaxillary mucins, antifreeze glycoprotein and alpha-1 acid glycoprotein as acceptors showed that the increased sialylation by CML extracts was due primarily to substrates with the O-linked Gal beta 1----3GaINAc acceptor group. These data suggest that sialyltransferase activity is increased in CML granulocytes compared to normal granulocytes and that the increased enzyme activity is specific for O-linked Gal beta 1----3GaINAc. This enzyme activity may be directly responsible for the abnormal membrane sialylation and pathophysiological behavior of these cells.
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PMID:Increased activity of a specific sialyltransferase in chronic myelogenous leukemia. 241 27

The pathway for synthesis of three glycosphingolipids bearing a common sialyl-Lex determinant (NeuAc alpha 2----3Gal beta 1----4[Fuc alpha 1----3]GlcNac beta 1----R) from their type 2 lactoseries precursors has been studied using the 0.2% Triton X-100-soluble fraction from human lung carcinoma PC9 cells. Two enzymes were found to be required for their synthesis: (i) an alpha 1----3 fucosyltransferase, the properties of which have been characterized as being similar to the enzyme from human small cell lung carcinoma NCI-H69 cells (Holmes, E. H., Ostrander, G. K., and Hakomori, S. (1985) J. Biol. Chem. 260, 7619-7627); and (ii) an alpha 2----3 sialyltransferase that was efficiently solubilized by 0.2% Triton X-100 and required divalent metal ions and 0.3% Triton CF-54 for optimal activity at pH 5.9 in cacodylate buffer. Biosynthesis of the sialyl-Lex determinant was shown to proceed via sialylation of nLc6 and nLc4, followed by alpha 1----3 fucosylation at the penultimate GlcNAc residues, based on the following: (i) transfer of NeuAc by PC9 cell sialyltransferase was found only when the nonfucosylated acceptors nLc4 and nLc6 were added, and none of the glycolipids with Lex structure (III3FucnLc4; V3FucnLc6; III3V3Fuc2nLc6) were sialylated; and (ii) the PC9 cell fucosyltransferase was active with both neutral and ganglioside neolacto (type 2 chain) acceptors. Transfer of fucose to VI3NeuAcnLc6 yielded mono- and difucosyl derivatives, whereas only a monofucosyl derivative was obtained when VI6NeuAcnLc6 was the acceptor. This is most probably due to different conformations at the terminus of the two acceptor gangliosides. The fucosyltransferase was incapable of transferring fucose to sialyl 2----3 lactotetraosylceramide (IV3NeuAcLc4).
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PMID:Biosynthesis of the sialyl-Lex determinant carried by type 2 chain glycosphingolipids (IV3NeuAcIII3FucnLc4, VI3NeuAcV3FucnLc6, and VI3NeuAcIII3V3Fuc2nLc6) in human lung carcinoma PC9 cells. 241 36

Human-murine myeloid somatic cell hybrids were assayed for the expression of the myeloid-associated sialyl-X determinant. This determinant is expressed at the surface of hybrid cells containing human chromosome 11, but its expression could not be correlated with the presence of the sialyltransferase which is involved in the sialyl-X synthesis. The sialyl-X determinant, however, is simultaneously expressed with another alpha 2----3-sialyltransferase activity, which is involved in the sialylation of the O-linked Gal beta 1----3GalNAc alpha-R core structure. Chromosomal analyses and enzymatic data suggest that human chromosome 11 is involved in the expression of both the sialyl-X antigen and this alpha 2----3-sialyltransferase.
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PMID:Specific expression of a myeloid-associated CMP-NeuAc:Gal beta 1----3GalNAc alpha-R alpha 2----3-sialyltransferase and the sialyl-X determinant in myeloid human-mouse cell hybrids containing human chromosome 11. 244 51

We present evidence for the existence in rat brain of several sialyltransferases able to sialylate sequentially asialofetuin. [14C]Sialylated glycans of asialofetuin were analyzed by gel filtration. Three types of [14C]sialylated glycans were synthesized: N-glycans and monosialylated and disialylated O-glycans. The varying effects of N-ethylmaleimide, lysophosphatidylcholine (lysoPtdCho) and trypsin, were helpful in the identification of these different sialyltransferases. One of them, selectively inhibited by N-ethylmaleimide, was identified as the Neu5Ac alpha 2----3Gal beta 1----3GalNAc-R:alpha 2----6 sialyltransferase previously described [Baubichon-Cortay, H., Serres-Guillaumond, M., Louisot, P. and Broquet, P. (1986) Carbohydr. Res. 149, 209-223]. This enzyme was responsible for the synthesis of disialylated O-glycans. LysoPtdCho and trypsin selectively inhibited the enzyme responsible for the synthesis of monosialylated O-glycan. N-ethylmaleimide, lysoPtdCho and trypsin did not inhibit Neu5Ac transfer onto N-glycans, giving evidence for three different molecular species. To identify the enzyme responsible for monosialylated O-glycan synthesis, we used another substrate: Gal beta 1----3GalNAc--protein obtained after galactosylation of desialylated ovine mucin by a GalNAc-R:beta 1----3 galactosyltransferase from porcine submaxillary gland. This acceptor was devoid of N-glycans and of NeuAc in alpha 2----3 linkages on the galactose residue. When using N-ethylmaleimide we obtained the synthesis of only one product, a monosialylated structure. After structural analysis by HPLC on SAX and SiNH2 columns, we identified this product as Neu5Ac alpha 2----3Gal beta 1----3GalNAc. The enzyme leading to synthesis of this monosialylated O-glycan was identified as a Gal beta 1----3GalNAc-R:alpha 2----3 sialyltransferase. When using lysoPtdCho and trypsin, sialylation was completely abolished, although the Neu5Ac alpha 2----3Gal beta 1----3GalNAc-R:alpha 2----6 sialyltransferase was not inhibited. We provided thus evidence for the interpendence between the two enzymes, the alpha 2----3 sialyltransferase regulates the alpha 2----6 sialyltransferase activity since it synthesizes the alpha 2----6 sialyltransferase substrate.
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PMID:Evidence for an O-glycan sialylation system in brain. Characterization of a beta-galactoside alpha 2,3-sialyltransferase from rat brain regulating the expression of an alpha-N-acetylgalactosaminide alpha 2,6-sialyltransferase activity. 247 71

The sialyltransferase activities of 10 human colorectal specimens were compared with those of the corresponding adjacent normal mucosa. Using asialofetuin as an acceptor we found, in tumor tissues of 9 out of 10 patients, an increased sialyltransferase activity towards the N-linked chains as determined upon peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase (PNGase) treatment. On the contrary, the activity towards the O-linked chains was not significantly changed. When the specificity of the sialyltransferase acting on N-linked chains was investigated by using N-acetyl-lactosamine (Gal beta 1,4GlcNAc) as an acceptor, we found that the alpha 2,6 sialyltransferase activity expressed by both normal and tumor colorectal tissues was far higher than the alpha 2,3-activity and that alpha 2,6 was the only sialyltransferase activity increased in tumor tissues. Kinetic analysis revealed that normal and tumor alpha 2,6 sialyltransferases have the same apparent Km for the acceptor substrate (469 and 465 microns), but normal enzyme has a higher Km for CMP-NeuAc (303 microns) than the tumor enzyme (50 microns). The higher affinity of tumor enzyme for the nucleotide-sugar might partially explain its increased activity in tumor tissues. In addition, tumor tissues contain a lower amount of sialic acid despite the increase in alpha 2,6 sialyltransferase activity.
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PMID:Increased CMP-NeuAc:Gal beta 1,4GlcNAc-R alpha 2,6 sialyltransferase activity in human colorectal cancer tissues. 247 2

Retinoic acid induced differentiation of TERA-2-derived human embryonal carcinoma cells is accompanied by a dramatic reduction of extended globo-series glycolipids, including galactosyl globoside, sialylgalactosyl globoside, and globo-A antigen (each recognized by specific MoAbs). Associated with these glycolipid changes, the activities of two key enzymes, alpha 1----4 galactosyltransferase (for synthesis of globotriaosyl core structure) and beta 1----3 galactosyltransferase (for synthesis of galactosyl globoside), were found to be reduced 3- to 4-fold. The latter enzyme plays a key role in the synthesis of extended globo-series structures, and its characterization has not been reported previously. Therefore, its catalytic activity was studied in detail, including substrate specificity, detergent and phospholipid effects, pH and cation requirements, and apparent Km. During retinoic acid induced differentiation, a series of Lex glycolipid antigens (recognized by anti-SSEA-1 antibody) and their core structures (lacto-series type 2 chains) increase dramatically. In parallel with these changes in glycolipid expression, the activities of two key enzymes, beta 1----3 N-acetylglucosaminyltransferase (for extension of lacto-series type 2 chain) and alpha 1----3 fucosyltransferase (for synthesis of Lex structure), were found to increase by 4- and 2-fold, respectively. Similarly, an increase in the expression of several gangliosides (e.g., GD3 and GT3) during retinoic acid induced differentiation was mirrored by a 4-fold increase in the activity of alpha 2----3 sialyltransferase (for synthesis of ganglio core structure, GM3). The results suggest a coordinate regulation of key glycosyltransferases involved in core structure assembly and terminal chain modification.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycolipid glycosyltransferases in human embryonal carcinoma cells during retinoic acid induced differentiation. 249 76


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