β3-Galactosyltransferase-I, -II, and -III
In higher eukaryotes, galactose is commonly found in all classes of glycoconjugates, where it is bound as either α- or β-anomer through 1,3- or 1,4-linkage to various carbohydrate acceptor substrates. Families of galactosyltransferases are defined according to the type of linkage catalyzed. Purification studies have suggested the existence of several enzymes in each galactosyltransferase family, assumptions which have been confirmed by the recent cloning of genes encoding galactosyltransferases. However, the number of galactosyltransferase genes isolated has far surpassed these early predictions. The characterization of the members of each galactosyltransferase family has revealed differences in the patterns of tissue expression and in acceptor substrate specificity, although a certain degree of redundancy prevails between galactosyltransferases from a given family. For example, four β3-galactosyltransferase (β3GalT) genes have been described that direct the expression of enzymes linking Galβ1,3 to GlcNAc (Hennet et al. 1998; Kolbinger et al. 1998; Amado et al. 1998; Isshiki et al. 1999; Zhou et al. 1999a). A comparison between β3GalT proteins unraveled several conserved domains not found in other galactosyltransferases. Surprisingly, a β3-N-acetylglucosaminyltransferase enzyme as well as proteins homologous to the Drosophila signaling proteins Brainiac and Fringe were also identified among the β3GalT-related proteins. β3GalTs participate in the shaping of several oligosaccharide structures in O-glycans, N-glycans and glycolipids. This review summarizes the properties of three β3GalT enzymes that direct the formation of type-1 chains, the support of Lea and Leb antigens.
KeywordsAcceptor Substrate Human Colonic Adenocarcinoma Cell Line Galt Activity Swine Trachea Galactosyltransferase Gene
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- Amado M, Almeida R, Carneiro F, Levery SB, Holmes EH, Nomoto M, Hollingsworth MA, Hassan H, Schwientek T, Nielsen PA, Bennett EP, Clausen H (1998) A family of human β-3-galactosyltransferases—characterization of four members of a UDP-galactose-β-N-acetylglucosamine/β-N-acetylgalactosamine β-1, 3-galactosyltransferase family. J Biol Chem 273:12770–12778PubMedCrossRefGoogle Scholar
- Holmes EH (1989) Characterization and membrane organization of β1,3-and β1,4-galactosyltransferases from human colonic adenocarcinoma cell lines Colo 205 and SW403: basis for preferential synthesis of type-1 chain lacto-series carbohydrate structures. Arch Biochem Biophys 270:630–646PubMedCrossRefGoogle Scholar
- Isshiki S, Togayachi A, Kudo T, Nishihara S, Watanabe M, Kubota T, Kitajima M, Shiraishi N, Sasaki K, Andoh T, Narimatsu H (1999) Cloning, expression, and characterization of a novel UDP-galactoseβ-N-acetylglucosamine β 1,3-galactosyltransferase (β3Gal-T5) responsible for synthesis of type-1 chain in colorectal and pancreatic epithelia and tumor cells derived therefrom. J Biol Chem 274:12499–12507PubMedCrossRefGoogle Scholar
- Nakamori S, Kameyama M, Imaoka S, Furukawa H, Ishikawa O, Sasaki Y, Kabuto T, Iwanaga T, Matsushita Y, Irimura T (1993) Increased expression of sialyl Lewis X antigen correlates with poor survival in patients with colorectal carcinoma: clinicopathological and immunohistochemical study. Cancer Res 53:3632–3637PubMedGoogle Scholar
- Sasaki K, Sasaki E, Kawashima K, Hanai N, Nishi T, Hasegawa M (1994) Beta-galactosyl-transferase DNA and protein—useful for production of saccharide chains. Japanese Patent JP 6181759Google Scholar
- Zhou D, Dinter A, Gutierrez Gallego R, Kamerling JP, Vliegenthart JFG, Berger EG, Hennet T (1999b) A β-1,3-N-acetylglucosaminyltransferase with poly-N-acetyllactosamine synthase activity is structurally related to β-1,3-galactosyltransferases. Proc Natl Acad Sci USA 96:406–411PubMedCrossRefGoogle Scholar