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)

We have previously shown that transferrin receptor (TfR) recycles from the cell surface through the Golgi complex in K562 human leukemia cells. However, little is known about the transport pathway that carries these receptors to the Golgi complex. To learn more about this transport, we studied the effects of treatments that block specific types of vesicular traffic. K562 cells were cultured in test media and the transport of surface TfR to the Golgi complex was assessed by measuring the entry of asialo-TfR into the sialyltransferase compartment of the Golgi complex. Depletion of cellular potassium, which blocks formation of coated vesicles at the cell surface, stimulated asialo-TfR resialylation by 60% over controls, suggesting that coated vesicle formation is not the rate-limiting step in cell surface-to-Golgi transport. Similarly, culture in sodium-free medium, which blocks transport from endosomes to lysosomes, increased asialo-TfR resialylation by 40%, arguing that lysosomes do not lie on the transport pathway. In contrast, incubation of cells in hypertonic medium, which blocks many vesicular transport steps, inhibited TfR resialylation by 40%, confirming the importance of vesicular traffic in transport of asialo-TfR from the cell surface to the Golgi complex. These results are consistent with two possible pathways for cell surface-to-Golgi transport. Receptor could be transported via an endosomal intermediate, with the rate-limiting step occurring at a post-endosomal site. Alternatively, receptor could be transported directly to the Golgi via a pathway that does not involve endosomes.
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PMID:Role of vesicular traffic in the transport of surface transferrin receptor to the Golgi complex in cultured human cells. 172 35

The role of acidic glycosphingolipids in cell growth and differentiation was investigated using the multipotent leukemia cell line K562. When GM3 was added to cell culture media, the growth of K562 cells was remarkably inhibited and the cells were shown to have megakaryocytoid morphology. Ultrastructural study demonstrated that K562 cells treated with GM3 had platelet peroxidase-positive structures, which were considered to be the specific marker of megakaryocyte. Furthermore, AP-3 directed against an epitope present on membrane glycoprotein IIIa reacted with the GM3-treated cells. Free N-acetylneuraminic acid, GM1, GM2, GD1a, and a mixture of bovine brain gangliosides containing GD1a and GT1b did not affect growth of K562 cells or show morphological changes. According to chemical analyses, GM3 content increased in megakaryocytoid differentiation induced by tetradecanoylphorbol-13-acetate, whereas GM3 decreased in erythroid differentiation induced by hemin. Enzymatic analysis showed that the GM3 increase during megakaryocytoid differentiation was a result of the sialyltransferase activation. These results indicated that exogenous GM3 induced differentiation of K562 cells into a "GM3-rich" lineage, i.e., mainly megakaryocytoid lineage, and that GM3 accumulation in the GM3-rich lineage was the result of the activation of GM3 synthase. These findings strongly suggested that GM3 ganglioside, a minor membrane component, has a crucial role in not only the differentiation induction but also the determination of the differentiation direction in pluripotent K562 cells.
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PMID:Ganglioside GM3 can induce megakaryocytoid differentiation of human leukemia cell line K562 cells. 200 80

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

The short-term incubation of rat thymocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a significant increase in sialyltransferase (S-T) activity and a decrease in terminal deoxyribonucleotidyl transferase (TdT) activity. The ratio of peanut agglutinin (PNA)-positive cells and of TdT-positive cells in TPA-treated cells also decreased. However, TPA had no significant effects on the viability, morphology, DNA synthesis, and DNA polymerase alpha activity of the cells. More marked changes were observed by incubating a non-T, non-B human lymphoid leukaemia cell line with TPA. Similar findings were also noted in TPA-treated mouse thymocytes. These changes may represent an aspect of TPA-induced differentiation of murine thymocytes.
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PMID:Effects of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on rat thymocytes. 278 10

The release of galactosyltransferase, sialyltransferase, and several glycosidase activities into the growth media from several normal and transformed cell lines was examined. Six of the seven cell lines released galactosyltransferase into their culture media. Only the human leukemia CCRF-CEM cells failed to release demonstrable galactosyltransferase activity. Release of galactosyltransferase activity into the media closely paralleled the growth curves for all but the BHKpy cells. These cells continued to release peak levels of galactosyltransferase activity into the culture media after their growth had plateaued. Media galactosyltransferase activity was unaffected by Triton X-100 treatment had remained in the supernatant fraction of a 100,000 X g, 12-hr centrifugation, suggesting that the cells release galactosyltransferase in a soluble form. In contrast to galactosyltransferase activity, only one of the cell lines (L1210) released sialyltransferase activity in appreciable amounts. Even this level of activity was 20-fold less than that observed for galactosyltransferase in the media from L1210 cells. Of the nine glycosidase activities assayed, only N-acetylglucosaminidase was observed in significant amounts in the media from all but the CCRF-CEM cells. However, N-acetylglucosaminidase release did not correlate closely with cell growth. These findings suggest a relatively specific release of galactosyltransferase and N-acetylglucosaminidase activities by cells in tissue culture. Moreover, the release of galactosyltransferase closely parallels cell growth. The significance of these released enzymes, especially to cell growth, has yet to be determined.
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PMID:Release of glycosyltransferase and glycosidase activities from normal and transformed cell lines. 678 58

In L1210 leukemia cells, 6-deoxy-6-fluoro-D-galactose specifically inhibited the incorporation of [3H]-D-galactose, while that of other precursors of glycoconjugate biosynthesis, including mannose and glucosamine, was unaffected. The activation of [6-3H]-6-deoxy-6-fluoro-D-galactose to a nucleotide sugar was similar to that found for [3H]-D-galactose. The incorporation of either sugar after 1 hr was visualized by electron microscopic autoradiography to be in the Golgi region. Treatment of L1210 cells with 6-deoxy-6-fluoro-D-galactose in vitro or in vivo resulted in a specific, dose- and time-dependent decrease in the activity of cell surface sialyltransferase (ectosialyltransferase) but not of 5'-nucleotidase, a plasma membrane marker enzyme. The decrease in ectosialyltransferase activity appeared to be selective and is suggested to be due to structural modification of the cell surface galactoprotein acceptors for this enzyme. The data indicate that 6-deoxy-6-fluoro-D-galactose is an effective modifier of cellular glycoconjugate in that its incorporation into certain cell surface components results in a modification of plasma membrane structure and function.
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PMID:Effects of a membrane sugar analogue, 6-deoxy-6-fluoro-D-galactose, on the L1210 leukemic cell ectosialyltransferase system. 684 4

The level of sialyltransferase activity in leukaemic blasts from acute lymphoblastic leukaemia (ALL) cases was significantly lower (3.29 +/- 2.09 pmoles/5 X 10(7) cells or 1.77 +/- 1.16 pmoles/mg protein) than those (18.80 +/- 4.91 pmoles/5 X 10(7) cells or 7.72 +/- 1.75 pmoles/mg protein) of mature lymphocytes from normal volunteers (T less than 0.001). An inverse relationship between the level of sialyltransferase activity and the level of terminal transferase (TdT)activity was seen in blasts from eight TdT-positive ALL cases. No significant difference was observed in the level of sialyltransferase activity between ALL and cells of chronic myelogenous leukemia (CML) in blast crisis. Short Term culture of ALL blast cells with 12-0-tetradecanoylphorbol-13-acetate (TPA) at the concentration of 10-(6)M to 10-(9)M caused a marked increase in sialyltransferase activity. In one of these three ALL cases the population of TdT-positive cells and the TdT activity of the blasts decreased significantly after culture with TPA. These results suggest that biochemical differentiation of leukaemic lymphoblasts has been induced by the addition of TPA, although morphological changes were not observed. Sialyltransferase activity may be a useful indicator for the analysis of differentiation of lymphocytes.
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PMID:Sialyltransferase activity as a marker for the differentiation of lymphocytes. Increase in sialyltransferase activity of blasts from acute lymphoblastic leukaemia cases by 12-o-tetradecanoylphorbol-13-acetate (TPA). 695 64

We have previously shown that erythroid differentiation of Friend murine leukemia cells by dimethylsulfoxide results in a decrease in sialic acid content and net negative surface charge. The mechanism responsible for the decrease in sialic acid content was examined by measuring the synthesis of sialic acid from N-acetylmannosamine and its catabolic removal from sialoconjugates during the maturation process. A decrease in the incorporation of N-[3H]acetylmannosamine into sialoglycoconjugates occurred as early as 12 h after exposure to dimethylsulfoxide. Radioactivity incorporated into sialoglycoconjugates was relatively stable in untreated and dimethyl-sulfoxide-treated cells, implying that catabolic removal of sialic acid residues was not a factor in the decreased surface sialic acid content of differentiated erythroleukemia cells. In addition, no difference existed between control and treated cells in sialyltransferase activity. Significant decreases occurred, however, in the incorporation of radioactivity from N-[3H]acetylmannosamine into N-acetylneuraminic acid, CMP-N-acetylneuraminic acid and a material tentatively identified as N-acetylmannosamine-6-phosphate, 48 h after the addition of dimethylsulfoxide. The decrease in sialic acid biosynthesis in differentiated erythroleukemia cells was reflected by an 83% decrease in the amount of radioactively-labeled sialic acid released by neuraminidase treatment of cells exposed to dimethylsulfoxide. These findings are consistent with a cellular aging phenomenon triggered by the polar solvent-induced differentiation of the leukemic cells into more mature forms.
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PMID:Synthesis of sialoglycoconjugates during dimethylsulfoxide-induced erythrodifferentiation of friend leukemia cells. 705 15

Plasma membrane glycoproteins recycle to the Golgi complex, but the route followed by these proteins is not known. To elucidate the pathway of transport, the involvement of clathrin-coated vesicles was tested. This was accomplished by comparing the traffic of wild type low density lipoprotein receptor (LDLR) and FH 683, a mutant receptor whose endocytosis from the cell surface in coated vesicles is reduced by 90-95%. Wild type LDLR traveled from the cell surface to the sialyltransferase compartment of the Golgi with a half-time of 2.5 h in K562 human leukemia cells expressing receptor from a transfected cDNA. In contrast, FH 683 LDLR recycled to the Golgi at 33% of the wild type rate, suggesting that wild type LDLR is largely transported to the Golgi by a pathway that involves clathrin-coated vesicles. Moreover, because clathrin-coated vesicles that bud from the plasma membrane are transported to endosomes, surface-to-Golgi transport probably involves an endosomal intermediate. Finally, because there was substantial transport of mutant LDLR to the Golgi even though its endocytosis in coated vesicles was greatly reduced, there may be a second pathway of surface-to-Golgi traffic. Our results suggest that wild type LDLR may move from plasma membrane to Golgi by two routes. Two-thirds of the traffic proceeds via a coated vesicle-mediated pathway while the remainder may follow a clathrin-independent pathway.
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PMID:Role of clathrin-coated vesicles in glycoprotein transport from the cell surface to the Golgi complex. 782 93

To elucidate control mechanisms of O-glycan biosynthesis in leukemia and to develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Gal beta 1-3GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (EC 2.4.1.102; core 2 beta 6-GlcNAc-T) and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase (EC 2.4.99.4; alpha 3-SA-T), two enzymes that are significantly increased in patients with chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic differences for the core 2 beta 6-GlcNAc-T activity; core 2 beta 6-GlcNAc-T from mucin secreting tissue (named core 2 beta 6-GlcNAc-T M) is accompanied by activities that synthesize core 4 [GlcNAc beta 1-6(GlcNAc beta 1-3)GalNAc-R] and blood group I [GlcNAc beta 1-6(GlcNAc beta 1-3)Gal beta-R] branches; core 2 beta 6-GlcNAc-T in leukemic cells (named core 2 beta-GlcNAc-T L) is not accompanied by these two activities and has a more restricted specificity. Core 2 beta 6-GlcNAc-T M and L both have an absolute requirement for the 4- and 6-hydroxyls of N-acetylgalactosamine and the 6-hydroxyl of galactose of the Gal beta 1-3GalNAc alpha-benzyl substrate but the recognition of other substituents of the sugar rings varies, depending on the tissue. alpha 3-sialyltransferase from human placenta and from AML cells also showed distinct specificity differences, although the enzymes from both tissues have an absolute requirement for the 3-hydroxyl of the galactose residue of Gal beta 1-3GalNAc alpha-Bn. Gal beta 1-3(6-deoxy)GalNAc alpha-Bn and 3-deoxy-Gal beta 1-3GalNAc alpha-Bn competitively inhibited core 2 beta 6-GlcNAc-T and alpha 3-sialyltransferase activities, respectively.
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PMID:Processing O-glycan core 1, Gal beta 1-3GalNAc alpha-R. Specificities of core 2, UDP-GlcNAc: Gal beta 1-3 GalNAc-R(GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase and CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase. 829 5


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