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

---

Query: EC:2.4.99.10 (sialyltransferase)
1,547 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganglioside GM3 is the predominant ganglioside of keratinocyte membranes. It has been proposed in other cell types that GM3 may participate in the regulation of cell proliferation. To examine the role of GM3 in keratinocyte proliferation, purified GM3 was added to cultured keratinocytes from normal foreskin, from lesional skin of patients with psoriasis and ichthyosis, and to cutaneous squamous carcinoma cell lines. Supplemental GM3 inhibited the growth of all cultured keratinocytes in a dose-dependent manner at concentrations of 10-100 microM. Keratinocytes from patients with psoriasis and ichthyosis were most sensitive to the inhibitory effects of GM3, and confluent undifferentiated keratinocytes were least sensitive. No change in differentiation was noted after addition of GM3. GD3, 9-0-acetyl-GD3, and GD1b also inhibited keratinocyte proliferation. Gangliosides GM1 and GD1a and sialic acid had little effect. Addition of 50 microM 3H-GM3 to cultured keratinocytes resulted in 1.7 times the amount of cellular GM3. These data suggest that hematoside (GM3) and "b" pathway gangliosides (GD3, GD1b), generated by the preferential activation of sialyltransferase II versus N-acetylgalactosaminyltransferase, may be involved in control of keratinocyte growth but not of differentiation.
...
PMID:Ganglioside GM3 inhibits the proliferation of cultured keratinocytes. 849 25

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.
...
PMID:Glycolipid acceptor specificity of a human Gal beta(1-3/1-4) GlcNAc alpha 2,3-sialyltransferase. 855 8

9-O-Acetylation of sialic acids shows cell type-specific and developmentally regulated expression in various systems. In a given cell type, O-acetylation can also be specific to a particular type of glycoconjugate. It is assumed that this regulation is achieved by control of expression of specific 9-O-acetyltransferases. However, it has been difficult to test this hypothesis, as these enzymes have so far proven intractable to purification or molecular cloning. During a cloning attempt, we discovered that while polyoma T antigen-positive Chinese hamster ovary cells (CHO-Tag cells) do not normally express cell-surface 9-O-acetylation, they do so when transiently transfected with a cDNA encoding the lactosamine-specific alpha2-6-sialyltransferase (Galbeta1-4GlcNAc:alpha2-6-sialyltransferase (ST6Gal I); formerly ST6N). This phenomenon is reproducible by stable expression of ST6Gal I in parental CHO cells, but not upon transfection of the competing lactosamine-specific alpha2-3-sialyltransferase (Galbeta1-(3)4GlcNAc:alpha2-3-sialyltransferase; (ST6Gal III) formerly ST3N) into either cell type. Further analyses of stably transfected parental CHO-K1 cells indicated that expression of the ST6Gal I gene causes selective 9-O-acetylation of alpha2-6-linked sialic acid residues on N-linked oligosaccharides. In a similar manner, while the alpha2-3-linked sialic acid residue of the endogenous GM3 ganglioside of CHO cells is not O-acetylated, transfection of an alpha2-8-sialyltransferase (GM3:alpha2-8-sialyltransferase (ST8Sia I); formerly GD3 synthase) caused expression of 9-O-acetylation of the alpha2-8-linked sialic acid residues of newly synthesized GD3. These data indicate either that linkage-specific sialic acid O-acetyltransferase(s) are constitutively expressed in CHO cells or that expression of these enzymes is secondarily induced upon expression of certain sialyltransferases. The former explanation is supported by a low level of background 9-O-acetylation found in parental CHO-K1 cells and by the finding that O-acetylation is not induced when the ST6Gal I or ST8Sia I cDNAs are overexpressed in SV40 T antigen-expressing primate (COS) cells. Taken together, these results indicate that expression of sialic acid 9-O-acetylation can be regulated by the action of specific sialyltransferases that alter the predominant linkage of the terminal sialic acids found on specific classes of glycoconjugates.
...
PMID:Linkage-specific action of endogenous sialic acid O-acetyltransferase in Chinese hamster ovary cells. 866 76

To address the role of alpha2,8-sialyltransferase (GD3 synthase) in the biosynthesis of gangliosides, we examined the substrate specificity of the enzyme. In the ganglioside synthesis pathway, it has been generally accepted that sialyltransferase II (SAT II) catalyzes the production of GD3 from GM3, and sialyltransferase V (SAT V) catalyzes the production of GD1c/GT1a/GQ1b from GM1h/GD1a/GT1b. However, acceptor specificity of the clones GD3 synthase that was isolated from human melanoma cells [Nara, K., Watanabe, Y., Maruyama, K., Kasahara, K., Nagai. Y. & Sanai, Y. (1994) Proc. Natl Acad. Sci. USA 91, 7952-7956] has revealed that this enzyme utilized the gangliosides containing the terminal Sia(alpha2-3)Gas structure of the carbohydrate moiety, which includes GM3, GM1b, GD1a and GT1B as exogenous substrates. Kinetic data also showed that the enzyme was able to utilize both GM3 and GM1b/GD1a/GT1b as acceptor substrates. These data indicate that the enzyme catalyzes the formation of not only GD3 but also GD1c, GT1a, and GQ1B in vitro. Furthermore, by transfection of the cloned human alpha2,8-sialyltransferase cDNA, transient and stable expression of GT1a and GQ1b wa also observed in COS-7 cells and Swiss 3T3 cells that originally lacked SAT II and SAT V activities. These observations indicate that the enzyme has both SAT II and SAT V activities in vivo.
...
PMID:Acceptor substrate specificity of a cloned GD3 synthase that catalyzes the biosynthesis of both GD3 and GD1c/GT1a/GQ1b. 870 63

The cDNAs encoding a new alpha2,8-sialyltransferase (ST8Sia V) were cloned from a mouse brain cDNA library by means of a polymerase chain reaction-based method using the nucleotide sequence information on mouse ST8Sia I (GD3 synthase) and mouse ST8Sia III (Siaalpha2,3Galbeta1,4GlcNAcalpha2,8-sialyltransferase ), both of which exhibit activity toward glycolipids. The predicted amino acid sequence of ST8Sia V shows 36.1% and 15.0% identity to those of mouse ST8Sia I and III, respectively. The recombinant protein A-fused ST8Sia V expressed in COS-7 cells exhibited an alpha2, 8-sialyltransferase activity toward GM1b, GD1a, GT1b, and GD3, and synthesized GD1c, GT1a, GQ1b, and GT3, respectively. The apparent Km values for GM1b, GD1a, GT1b and GD3 were 1.1, 0.082, 0.070, and 0.28 mM, respectively. However, ST8Sia V did not exhibit activity toward GM3. Thus, the substrate specificity of ST8Sia V is different from those of ST8Sia I and III, both of which exhibit activity toward GM3. Transfection of the ST8Sia V gene into COS-7 cells, which express GD1a as a major glycolipid, led to the expression of determinants for monoclonal antibody 4F10, which recognizes GT1a and GQ1b, suggesting that ST8Sia V exhibits activity toward gangliosides GD1a and/or GT1b in vivo. The expression of the ST8Sia V gene was tissue- and developmental stage-specific, and was clearly different from those of other alpha2,8-sialyltransferase genes. The ST8Sia V gene was strongly expressed in the brain and weakly in other tissues such as the liver. In addition, its expression was greater in the adult than fetal brain. These results strongly indicate that ST8Sia V is a candidate for SAT-V, the alpha2,8-sialyltransferase involved in GD1c, GT1a, GQ1b, and GT3 synthesis.
...
PMID:Molecular cloning and expression of a fifth type of alpha2,8-sialyltransferase (ST8Sia V). Its substrate specificity is similar to that of SAT-V/III, which synthesize GD1c, GT1a, GQ1b and GT3. 891 Jun

In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-gamma increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.
...
PMID:Alteration of human melanoma gangliosides by IFN-gamma, IL-2, and IL-4. 893 35

A trimeric beta-lactosyl cluster based on 2-nitro-2-(hydroxymethyl)propane-1,3-diol was prepared using the trichloroacetimidate method. Kinetic studies showed that this cluster was an effective acceptor for rat-liver alpha-(2-->3)-sialyltransferase. Its KM was comparable to those for monomeric lactose and N-acetyllactosamine acceptors, and its Vmax was 1% of that measured for the LacNAc acceptor. Preparative-scale sialylation using this enzyme afforded a trimeric cluster of the ganglioside GM3 oligosaccharide in good yield. The NMR spectra of the trimeric GM3 analogue suggest that the oligosaccharide conformation is not significantly perturbed by this level of clustering.
...
PMID:Chemoenzymatic synthesis of a trimeric ganglioside GM3 analogue. 922 35

A 2.1-kb 5'-flanking fragment of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase (GD3-synthase) gene was cloned by the genomic walking procedure. The promoter activity of the fragment was assessed in F-11 cells by transient transfection and the locations for the basal and maximal promoter activities were defined. Primer extension analysis identified a transcription start site approximately 98 bp upstream of the ATG start codon. DNA sequence analysis of the promoter revealed a number of consensus binding sites for known transcription factors such as SP1, AP1, NFkappaB, C/EBP and TFIID, and a repeat GC-GT sequence motif seen for the formation of Z-type DNA. Both TATA and CCAAT boxes were not found in the promoter. Our results from deletion constructs suggested that both positive and negative cis-acting regulatory regions were present in this TATA-less promoter of the rat GD3-synthase gene.
...
PMID:Isolation and functional analysis of the promoter of the rat CMP-NeuAc:GM3 alpha2,8 sialyltransferase gene 1. 956 65

Castrated male rats were subcutaneously injected testosterone (5 and 10 mg) or a mixture of beta-estradiol and progesterone (1 microg + 2 mg), to determine whether sex steroid hormones (testosterone, beta-estradiol, progesterone) might affect the content of sialoglycoproteins, the content and pattern of lipid-bound sialic acid, and the activities of sialyltransferase (SAT) I and SAT II in the Golgi-rich membrane fraction isolated from rat kidney. During four days testosterone did not affect significantly the content of proteins, sialoglycoproteins and total gangliosides, but increased the content of b-series gangliosides from 0.05 +/- 0.006 (untreated animals injected subcutaneously with 0.1 ml DMSO for four days) to 0.16 +/- 0.02 nmol sialic acid (SA) per mg protein (castrated animals injected subcutaneously with 10 mg testosterone/0.1 ml DMSO for four days). This increase was due to the increase in GD3 ganglioside from 0.03 to 0.12 nmol SA/mg protein, and to the decrease of GM3 ganglioside from 0.06 to 0.03 nmol SA/mg protein by testosterone administration. The major ganglioside in the rat kidney was GM3, constituting 63% (control group) and 51% (castrated animals injected daily with 10 mg testosterone) of all gangliosides. Castration itself induced an increase in the rat kidney SAT I and SAT II activities from 712 +/- 130 to 1723 +/- 412 pmol/h x mg protein and from 208 +/- 48 to 751 +/- 176 pmol/h x mg protein, respectively. However, subsequent administration of testosterone, at the highest concentration tested, reversed this effect. In the kidneys of castrated rats, a mixture of beta-estradiol and progesterone decreased SAT II activity from 208 +/- 48 to 87 +/- 33 pmol/h x mg protein.
...
PMID:The influence of sex steroid hormones on ganglioside biosynthesis in rat kidney. 968 18

Cell differentiation is frequently accompanied by alterations in the composition of gangliosides in the plasma membrane resulting from a regulation of the enzyme activities involved. The regulation of CMP-NeuAc:GM1 alpha2-3-sialyltransferase (ST-IV) and UDP-GalNAc:GM3 N-acetylgalactosaminyltransferase (Gal-NAc-T) by the degree of enzyme phosphorylation was analyzed by determination of the enzyme activity on incubation of NG108-15 cells with various protein phosphatase inhibitors (okadaic acid and orthovanadate) or protein kinase activators (phorbol ester and forskolin). Incubation with okadaic acid, but not with orthovanadate, inhibited the ST-IV activity to 45% of that of control cells with t(1/2) = 60 min for the inactivation reaction. This indicates a rapid hyperphosphorylation of ST-IV due to the inhibition of a serine/threonine-specific phosphatase. A similar rate of inactivation was found on stimulation of protein kinase C with phorbol ester. In contrast to ST-IV, the activity of GalNAc-T was increased on stimulation of intracellular phosphorylation systems. The fastest activation of GalNAc-T was achieved with forskolin, yielding up to 160% of the initial activity within 30 min of effector incubation. Up-regulation of GalNAc-T in conjunction with down-regulation of ST-IV by stimulation of phosphorylation is suggested to serve as a physiological mechanism to increase the concentration of GM1, which was found to be elevated in correlation with the cell density. This assumption was corroborated by metabolic labeling studies with radioactive ganglioside precursors indicating an enhancement of the relative amount of a-series gangliosides subsequent to GM3 on phosphorylation stimulation. In particular, the biosynthesis of GM1 was specifically elevated within 2 h of incubation with forskolin. We conclude from the overall data that the ganglioside composition during the cell differentiation of NG108-15 cells can be specifically regulated by both protein kinase A- and protein kinase C-related phosphorylation systems.
...
PMID:Regulation of ganglioside metabolism by phosphorylation and dephosphorylation. 972 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---