Disease relevance of GGTA1

• Characterization of products synthesized by galactosyltransferase purified from the ascites of ovarian cancer patients [1].
• These results suggest that the galactosyltransferase from the ascites of ovarian cancer patients catalyzes the transfer of galactose to N-acetylglucosamine, irrespective of whether it is a part of an N-glycan or an O-glycan [1].
• A 149-kDa virion protein of human strains of cytomegalovirus is the principal acceptor for galactose added in vitro by bovine milk galactosyltransferase [2].
• For this study, a murine GalTase clone was obtained by screening a lambda gt10 cDNA library made from F9 embryonal carcinoma cells with a heterologous bovine GalTase cDNA probe [3].
• The galactosyltransferase activities in tissue homogenates from both carcinomas were higher than in adjacent normal control with asialoagalactofetuin as a substrate [4].

High impact information on GGTA1

• Drosophila polytene chromosomes contain a surprisingly large amount of terminal N-acetylglucosamine (GlcNAc) residues along their lengths, as determined by staining with a fluorescently tagged lectin, wheat germ agglutinin (FITC-WGA) and by specific radio-labeling with bovine galactosyltransferase and UDP-[3H]galactose [5].
• They contain significantly lower levels of enzyme activities representative of the plasma membrane (5' nucleotidase) or the Golgi complex (galactosyltransferase and sialyltransferase) [6].
• It has been proposed that GalTase participates during migration by recognizing and binding to terminal N-acetylglucosamine (GlcNAc) residues on glycoconjugates within the extracellular matrix (Shur, B. D., 1982, Dev. Biol. 91:149-162) [7].
• Second, the addition of competitive GalTase substrates significantly inhibited neural crest cell migration on basal lamina-like matrices, but as above, had no effect on migration on fibronectin [7].
• Quantitative enzyme assays confirmed the presence of GalTase substrates in basal lamina matrices, their absence in fibronectin matrices, and the ability of alpha-LA to inhibit GalTase activity towards basal lamina substrates [7].

Chemical compound and disease context of GGTA1

• In this work, we demonstrate that the wbbD gene of the O7 lipopolysaccharide (LPS) biosynthesis cluster in Escherichia coli strain VW187 (O7:K1) encodes a galactosyltransferase involved in the synthesis of the O7-polysaccharide repeating unit [8].
• Electrophoretic analysis of glycoprotein glycans produced by lepidopteran insect cells infected with an immediate early recombinant baculovirus encoding mammalian beta1,4-galactosyltransferase [9].

Biological context of GGTA1

• Bovine alpha 1----3-galactosyltransferase: isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA [10].
• Cell surface GalTase activity was perturbed using three independent sets of reagents, and the effects on cell migration were analyzed by time-lapse microphotography [7].
• Portions of the predicted amino acid sequence matched the six tryptic peptides isolated from affinity-purified bovine galactosyltransferase [11].
• Two synthetic oligonucleotides, 27mer and 21mer, were synthesized, based on the amino acid sequences of two peptides derived from bovine milk N-acetylglucosaminide (beta 1-4)galactosyltransferase (EC 2.4.1.90), and used as hybridization probes to isolate cDNA clones for galactosyltransferase from a bovine mammary gland cDNA library [12].
• In the Golgi apparatus, GalTase participates in the glycosylation of secretory and membrane-bound glycoproteins, whereas on the cell surface it mediates specific aspects of intercellular adhesion [3].

Anatomical context of GGTA1

• This enzyme is larger in molecular weight than previously studied soluble galactosyltransferases, but resembles in size the galactosyltransferase of lactating mammary Golgi membranes [13].
• Laminin was found to be a principle GalTase substrate in the basal lamina, and when tested in vitro, alpha-LA inhibited cell migration on laminin [7].
• Staining for galactosyltransferase was juxtanuclear and crescent shaped in epitheloid cells; a similar staining, occasionally perinuclear and sparsely distributed in the cytoplasm, was found in fibroblasts [14].
• The murine GalTase cDNA probe was used in conjunction with assays of GalTase activity to investigate the expression and distribution of GalTase during differentiation of F9 stem cells into secretory endodermal epithelium [3].
• Sedimentation velocity ultracentrifugation and other procedures have been used to investigate macromolecular interactions of bovine colostrum galactosyltransferase with a glycoprotein substrate (ovalbumin) and with the lactose synthase regulatory protein, alpha-lactalbumin [15].

Associations of GGTA1 with chemical compounds

• UDP-galactose:beta-galactosyl alpha-1,3-galactosyltransferase (alpha3GT) catalyzes the transfer of galactose from UDP-alpha-d-galactose into an alpha-1,3 linkage with beta-galactosyl groups in glycoconjugates [16].
• Third, addition of the GalTase catalytic substrate, UDPgalactose, produced a dose-dependent increase in the rate of cell migration [7].
• Bovine galactosyltransferase (lactose synthase; EC 2.4.1.22) which catalyzes the transfer of galactose from UDPgalactose to glycoproteins with N-acetylglucosamine as the terminal residue of their oligosaccharide side chains was used to label glycoproteins of mouse retina with [14C]galactose [17].
• We demonstrate that the Na(+)-pump alpha-subunit polypeptide is glycosylated by using bovine milk galactosyltransferase, a specific enzyme which attaches galactose to terminal N-acetylglucosamine residues [18].
• A comparison of the interactions of galactosyltransferase with a glycoprotein substrate (Ovalbumin) and with alpha-lactalbumin [15].

Physical interactions of GGTA1

• The results suggest that cell surface Gal Tase interacts with a form of the EGF-R, having altered carbohydrate moieties to promote intracellular signaling for acinar cell proliferation [19].

Other interactions of GGTA1

• The influence of compounds that might modulate the reaction was also examined. alpha-Lactalbumin, a modifier of the galactosyltransferase in milk, acted as a competitive inhibitor of the galactosylation of opsin [20].
• Together, these experiments show that neural crest cells have at least two distinct mechanisms for interacting with the substrate during migration, one that is fibronectin-dependent and one that uses GalTase recognition of basal lamina glycoconjugates [7].
• A 1.3-kilobase cDNA clone (7A) coding for bovine galactosyltransferase (glycoprotein 4-beta-galactosyltransferase, EC 2.4.1.38) was isolated from a lambda gt11 expression library by immunological screening with monospecific polyclonal antisera to the affinity-purified bovine enzyme [11].
• The beta-elimination of galactosyltransferase radiolabeled synapsin I and subsequent analysis of released saccharide on high-voltage paper electrophoresis confirmed the presence of monosaccharidic GlcNAc moieties in O-linkage to the protein [21].
• Galactosyltransferase, assayed as a lactose synthetase, showed a 10-fold greater affinity for glucose when Mn2+ ions were replaced by clupeine or by ribonuclease as cationic activator [22].

Analytical, diagnostic and therapeutic context of GGTA1

• However, by Southern blot analysis, homologous sequences for alpha 1----3-galactosyltransferase were identified in human genomic DNA [10].
• A galactosyltransferase, which transfers galactose from UDP-galactose to N-acetylglucosamine, was purified 286,000-fold to homogeneity with 40% yield from human plasma by repeated affinity chromatography on alpha-lactalbumin-Sepharose [23].
• In indirect immunofluorescence microscopy affinity-purified IgGs locate the galactosyltransferase in a distinct perinuclear and juxtanuclear position indicative for the Golgi region [24].
• Circular dichroism changes in galactosyltransferase upon substrate binding; [25].
• An ESR titration of UDP-R with galactosyltransferase at pH 8.0 yielded direct physical dissociation constants of 0.40 +/- 0.07 and 0.53 +/- 0.08 mM in the absence and presence of alpha-lactalbumin, respectively [26].

References