RRC ID |
67401
|
著者 |
Togayachi A, Akashima T, Ookubo R, Kudo T, Nishihara S, Iwasaki H, Natsume A, Mio H, Inokuchi J, Irimura T, Sasaki K, Narimatsu H.
|
タイトル |
Molecular cloning and characterization of UDP-GlcNAc:lactosylceramide beta 1,3-N-acetylglucosaminyltransferase (beta 3Gn-T5), an essential enzyme for the expression of HNK-1 and Lewis X epitopes on glycolipids.
|
ジャーナル |
J Biol Chem
|
Abstract |
A new member of the UDP-N-acetylglucosamine:beta-galactose beta1,3-N-acetylglucosaminyltransferase (beta3Gn-T) family having the beta3Gn-T motifs was cloned from rat and human cDNA libraries and named beta3Gn-T5 based on its position in a phylogenetic tree. We concluded that beta3Gn-T5 is the most feasible candidate for lactotriaosylceramide (Lc(3)Cer) synthase, an important enzyme which plays a key role in the synthesis of lacto- or neolacto-series carbohydrate chains on glycolipids. beta3Gn-T5 exhibited strong activity to transfer GlcNAc to glycolipid substrates, such as lactosylceramide (LacCer) and neolactotetraosylceramide (nLc(4)Cer; paragloboside), resulting in the synthesis of Lc(3)Cer and neolactopentaosylceramide (nLc(5)Cer), respectively. A marked decrease in LacCer and increase in nLc(4)Cer was detected in Namalwa cells stably expressing beta3Gn-T5. This indicated that beta3Gn-T5 exerted activity to synthesize Lc(3)Cer and decrease LacCer, followed by conversion to nLc(4)Cer via endogenous galactosylation. The following four findings further supported that beta3Gn-T5 is Lc(3)Cer synthase. 1) The beta3Gn-T5 transcript levels in various cells were consistent with the activity levels of Lc(3)Cer synthase in those cells. 2) The beta3Gn-T5 transcript was presented in various tissues and cultured cells. 3) The beta3Gn-T5 expression was up-regulated by stimulation with retinoic acid and down-regulated with 12-O-tetradecanoylphorbol-13-acetate in HL-60 cells. 4) The changes in beta3Gn-T5 transcript levels during the rat brain development were determined. Points 2, 3, and 4 were consistent with the Lc(3)Cer synthase activity reported previously.
|
巻・号 |
276(25)
|
ページ |
22032-40
|
公開日 |
2001-6-22
|
DOI |
10.1074/jbc.M011369200
|
PII |
S0021-9258(20)78469-3
|
PMID |
11283017
|
MeSH |
Amino Acid Sequence
Animals
Base Sequence
Cloning, Molecular
DNA, Complementary
Epitopes / chemistry*
Glycolipids / chemistry*
Humans
Lewis X Antigen / chemistry*
Molecular Sequence Data
N-Acetylglucosaminyltransferases / chemistry
N-Acetylglucosaminyltransferases / genetics*
N-Acetylglucosaminyltransferases / metabolism
Phylogeny
Rats
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Homology, Amino Acid
Tumor Cells, Cultured
|
IF |
4.238
|
リソース情報 |
ヒト・動物細胞 |
EBC-1(RCB1965)
MKN1(RCB1003)
MKN7(RCB0999)
MKN45(RCB1001) |