Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sialyl Lewis a/sialyl Lewis x antigens, which panels of monoclonal antibodies can recognize, are synthesized by a series of glycosyltransferases. Especially, alpha (1,3)/(1,4) fucosyltransferases and/or alpha(2,3)sialyltransferases regulate expression patterns temporally and spatially, such as in epithelium of digestive systems or in leukocytes. The carbohydrate ligands of P-selectin and E-selectin have been identified as sialyl Lewis x expressed on granulocytes, monocytes, and natural killer cells. Expression of sialyl Lewis x on these cells is mainly determined by Fuc-TVII, but as for the counterparts of sialyl-transferases, there remains much uncertainty. P-selectin-dependent adhesion of tumor cells and E-selectin-dependent adhesion of tumor cells to endothelial cells play some role for tumor cell aggregation leading to microembolism and hematogenous metastasis of cancers. We have found expression of some fucosyltransferases (Fuc-TIII, VI, VII) and a sialyltransferase (ST3O) are increased in colon cancer tissues coincidentally with sialyl Lewis a antigens, with which E-selectin can interact. As already started in many laboratories, genetic manipulation of glycosylation pathways in gene-targeted animals has an outstanding potential to yield clues to oligosaccharide function.
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PMID:[Structures, synthesis and functions of sialyl Le(a)/sialyl Le(x) antigens]. 763 14

Sialyl-Lewisx (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha 1-->3]GlcNAc] has been identified as a ligand for E-selectin, P-selectin and recently also for L-selectin. We have synthesized the sialyl-Lewisx tetrasaccharide by total enzymatic synthesis from N-acetyllactosamine using a placental alpha 2-->3-sialyltransferase specific for type-2 chain acceptors, followed by a cloned human alpha 1-->3-fucosyltransferase (FucTV, the 'plasma-type' enzyme). This procedure resulted in the tetrasaccharide in a 61% overall yield.
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PMID:Efficient enzymatic synthesis of the sialyl-Lewisx tetrasaccharide. A ligand for selectin-type adhesion molecules. 769 Jul 13

Activated Th1 CD4 T cells bind to P-selectin and migrate into inflamed tissue, whereas Th2 cells do not. We show that alpha(1, 3)-fucosyltransferase VII (FucT-VII) and alpha(2, 3)-sialyltransferase IV (ST3GalIV), which are crucial for the biosynthesis of functional P-selectin ligands, are absent in naive CD4 T cells, but are rapidly up-regulated upon activation. Th1 or Th2 differentiation in the presence of polarizing cytokines leads to down-regulation of FucT-VII mRNA selectively in Th2 but not in Th1 cells. Influencing the differentiation by varying the priming dose of antigenic peptide results in similar FucT-VII down-regulation only in Ag-specific Th2 cells. ST3GalIV levels remain elevated. FucT-VII and ST3GalIV mRNAs are also up-regulated by Th1 cells primed in vivo and recruited into the lymph nodes draining delayed-type hypersensitivity sites. We identify FucT-VII gene expression as a principal difference between Th1 and Th2 cells, and underscore the importance of FucT-VII and ST3GalIV expression for the biosynthesis of functional selectin ligands.
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PMID:Alpha(1,3)-fucosyltransferase VII and alpha(2,3)-sialyltransferase IV are up-regulated in activated CD4 T cells and maintained after their differentiation into Th1 and migration into inflammatory sites. 1049 Sep 70

The beta 1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to the cis/medial-Golgi compartment. To analyze the Golgi-targeting determinants of C2GnT, we constructed various deletion mutants of the enzyme fused to the enhanced green fluorescent protein (EGFP) and localized these proteins by fluorescence microscopy in living cells. We found that the N-terminal peptide encompassing amino acids 1 to 32 represents the minimal Golgi-targeting signal sufficient to localize EGFP to the same compartment as the full-length C2GnT. This peptide makes up the cytoplasmic and the transmembrane domains of the enzyme and was referred to as CTd (cytoplasmic and transmembrane domains). We compared the Golgi-targeting efficiency of the C2GnT-derived CTd with its homologous domains from other glycosyltransferases, including the H-type alpha(1,2)-fucosyltransferase (FucTI), the polypeptide N-acetylgalactosaminyltransferase-I (GalNAcT-I), the alpha(1,3)-fucosyltransferase VII (FucTVII), and the alpha(2,6)-sialyltransferase (ST6Gal-I) and found that the Golgi-targeting determinants of these glycosyltransferases were also composed of their cytosolic and transmembrane domains. To investigate whether the CTd of C2GnT could serve as a cis to medial Golgi-specific signal, we tested its ability to mislocalize two late-Golgi acting glycosyltransferases FucTI and FucTVII. We show that fusing the C2GnT-derived CTd with the catalytic domain of FucTVII resulted in a complete mislocalization of the enzyme to the C2GnT compartment, with a parallel alteration of sialyl-Lewis x synthesis and P-selectin binding. The intracellular distribution and activity of FucTI, however, were not affected. Thus, CTds of either early or late-Golgi acting glycosyltransferases represent the Golgi-targeting domains of these enzymes. In addition, we show that C2GnT-derived CTd can function as a cis/medial Golgi-targeting determinant.
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PMID:The cytosolic and transmembrane domains of the beta 1,6 N-acetylglucosaminyltransferase (C2GnT) function as a cis to medial/Golgi-targeting determinant. 1182 83

A variety of human adenocarcinomas express sialylated, fucosylated Lewis blood group antigens on cell surface and secreted mucins. Binding of these antigens to P-selectin on platelets is thought to facilitate formation of platelet-tumor emboli in the circulation, which in turn allows sequestration of the tumor cells in the microvasculature. Here we report a pharmacologic approach for blocking these interactions through metabolic inhibition of sialylation. Peracetylated forms of Galbeta1,4GlcNAcbeta-O-naphthalenemethanol and GlcNAcbeta1,3Galbeta-O-naphthalenemethanol were taken up by LS180 human colon carcinoma cells, O-deacetylated, and utilized as biosynthetic intermediates, resulting in heterogeneous oligosaccharides. The primed oligosaccharides included sialylated, sulfated, and fucosylated products based on mass spectrometry. Assembly of free oligosaccharides on the glycosides decoyed glycosylation of cellular glycoproteins, as assessed by altered binding of lectins and carbohydrate-specific antibodies. Expression of alpha2,3-sialylated oligosaccharides on the cell surface was diminished specifically, whereas alpha2,6-sialylation and fucosylation were not. In U937 lymphoma cells, the glycosides decreased fucosylation without affecting sialylation. The differential inhibitory activities correlated inversely with fucosyltransferase and sialyltransferase activity based on enzyme assays and microarray analysis. Regardless of the mechanism, the disaccharides blocked the cells from forming selectin ligands and inhibited adhesion to immobilized selectins, suggesting that the glycosides might prove useful for interfering with tumor cell adhesion and metastasis.
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PMID:Expression patterns of alpha 2,3-sialyltransferases and alpha 1,3-fucosyltransferases determine the mode of sialyl Lewis X inhibition by disaccharide decoys. 1268 49

T lymphocytes are important players in beneficial and detrimental immune responses. In contrast to other lymphocyte populations that develop in the bone marrow, T-cell precursors need to migrate to the thymus for further development. The interaction of P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) is crucial for thymic entry of T-cell precursors during settings of T-cell lineage reconstitution. PSGL-1 has to be sialylated to function as a ligand for P-selectin, and the sialyltransferase ST3Gal-IV might play a critical role in this process. We therefore investigated the role of ST3Gal-IV for T-cell development using competitive mixed bone marrow chimeric mice. We found that ST3Gal-IV is dispensable for homing and engraftment of hematopoietic precursors in the bone marrow. However, ST3Gal-IV deficiency affects seeding of the thymus by early T-cell progenitors, leading to impaired restoration of the peripheral T-cell compartment. This defect could be restored by ectopic retroviral expression of ST3Gal-IV in hematopoietic stem cells derived from ST3Gal-IV-deficient donor mice. Our findings show that ST3Gal-IV plays a critical and nonredundant role for efficient T-cell lineage reconstitution after bone marrow transplantation.
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PMID:The sialyltransferase ST3Gal-IV guides murine T-cell progenitors to the thymus. 3238 May 39