β4-Galactosyltransferase-II, -III, -IV, -V, -VI, and -VII
The Galβ1→4GlcNAc structure is commonly found in the outer chain moieties of N-and O-linked oligosaccharides, and in the oligosaccharides of lacto-series glycolipids. The terminal galactose itself is involved in galectin-mediated biological events, including apoptosis (Perillo et al. 1995), and many biologically active carbohydrate determinants involved in cell adhesion processes, such as polysialic acid, HNK-1 carbohydrate, poly-N-acetyllactosamine, Lewis X, and sialyl Lewis X, are expressed on the disaccharide groups. Therefore, β4-galactosyltransferase (β4GalT), which transfers galactose from UDP-Gal to N-acetylglucosamine, is one of the key enzymes in glycobiology. Targeted inactivation of the mouse β4GalT gene showed that the galactose and/or galactose-containing oligosaccharides are important for cell growth and differentiation, and that murine cells contain another β4GalT which produces the residual Galβ1→4GlcNAc groups found in the N-linked oligosaccharides of the mutant mouse (Asano et al. 1997; Kido et al. 1998; Lu et al. 1997). Since Lewis X-containing oligosaccharides inhibited the compaction of mouse embryos (Bird and Kimber 1984), and since a β4GalT-knockout mouse can survive beyond birth (Asano et al. 1997; Lu et al. 1997), the galactose-containing oligosaccharides synthesized by novel β4GalT could be important for the early development of mammalian embryos. To date, six novel human genes, five novel mouse genes, one novel rat gene, and one novel chicken gene which encode proteins with β4GalT activity have been cloned (see databank) (reviewed by Amado et al. 1999; Furukawa and Sato 1999). In addition to these, the mouse contains one more gene (accession No. D3779) which encodes a protein with β4GalT activity toward N-acetylglucosamine (Uehara and Muramatsu 1997). However, this enzyme is totally different from β4GalT-I-VII based on the sequence similarities. There are also several genes homologous to mammalian β4GalTs in invertebrates such as the nematode and snail (reviewed by Lo et al. 1998; Amado et al. 1999). This review mainly summarizes the properties of six novel human β4GalTs, although their acceptor specificities have not yet been established.
KeywordsPolysialic Acid Short Sequence Motif Cell Adhesion Process Search Nucleotide Sequence Transferase Gene Family
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- Almeida R, Amado M, David L, Levery SB, Holmes EH, Merkx G, van Kessel AG, Rygaard E, Hassan H, Bennett E, Clausen H (1997) A family of human β4-galactosyltransferases: cloning and expression of two novel UDP-galactose:β-N-acetylglucosamine β1,4-galactosyltransferases, β4Gal-T2 and β4Gal-T3. J Biol Chem 272:31979–31991PubMedCrossRefGoogle Scholar
- Almeida R, Levery SB, Mandel U, Kresse H, Schwientek T, Bennett EP, Clausen H (1999) Cloning and expression of a proteoglycan UDP-galactose:β-xylose β1,4-galactosyl-transferase I. A seventh member of the human β4-galactosyltransferase gene family. J Biol Chem 274:26165–26171PubMedCrossRefGoogle Scholar
- Guo S, Sato T, Shirane K, Furukawa K (2001) Galactosylation of N-linked oligosaccharides by human β-1,4-galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells. Glycobiology, in pressGoogle Scholar
- Sato T, Shirane K, Furukawa K (1999) Changes in β-1,4-galactosylation of glycoproteins in malignantly transformed cells. Recent Res Dev Cancer 1:105–114Google Scholar
- Sato T, Guo S, Furukawa K (2000) Involvement of recombinant human β-1,4-galactosyl-transferase V in lactosylceramide biosynthesis/Res Commun Biochem Cell Mol Biol 4:3–10Google Scholar
- Ujita M, McAuliffe J, Schwientek T, Almeida R, Hindsgaul O, Clausen H, Fukuda M (1998) Synthesis of pory-N-acetyllactosamine in core 2-branched O-glycans: the requirement of novel β-1,4-galactosyltransferase IV and β-1,3-N-acetylglucosaminyltransferase. J Biol Chem 273:34843–34849PubMedCrossRefGoogle Scholar
- Ujita M, Misra AK, McAuliffe J, Hindsgaul O, Fukuda M (2000) Poly-N-acetyllactosamine extention in N-glycans and core 2-and core 4-branched O-glycans is differentially controlled by I-extension enzyme and different members of the β1,4-galactosyl-transferase gene family. J Biol Chem 275:15868–15875PubMedCrossRefGoogle Scholar
- Yoshimi Y, Sato T, Ikekita M, Guo S, Furukawa K (2000) Presence of monoantennary complex-type and hybrid-type oligosaccharides terminated with β-N-acetylglu-cosamine in lepidopteran insect Sf-9 cells. Res Commun Biochem Cell Mol Biol 4:163–170Google Scholar