1999年5月14日
The tumor suppressor EXT-like gene EXTL2 encodes an α1, 4-N- acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N- acetylglucosamine to the common glycosaminoglycan-protein linkage region: The key enzyme for the chain initiation of hepa
Journal of Biological Chemistry
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- ,
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- 巻
- 274
- 号
- 開始ページ
- 13933
- 終了ページ
- 13937
- DOI
- 10.1074/jbc.274.20.13933
We previously demonstrated a unique α-N- acetylgalactosaminyltransferase that transferred N-acetylgalactosamine (GalNAc) to the tetrasaccharide-serine, GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O- Ser (GlcA represents glucuronic acid), derived from the common glycosaminoglycan-protein linkage region, through an α1,4-linkage. In this study, we purified the enzyme from the serum-free culture medium of a human sarcoma cell line. Peptide sequence analysis of the purified enzyme revealed 100% identity to the multiple exostoses-like gene EXTL2/EXTR2, a member of the hereditary multiple exostoses (EXT) gene family of tumor suppressors. The expression of a soluble recombinant form of the protein produced an active enzyme, which transferred α-GalNAc from UDP-[ 3 H]GalNAc to various acceptor substrates including GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser. Interestingly, the enzyme also catalyzed the transfer of N-acetylglucosamine (GlcNAc) from UDP-[ 3 H]GlcNAc to GlcAβ1-3Galβ1-O-naphthalenemethanol, which was the acceptor substrate for the previously described GlcNAc transferase I involved in the biosynthetic initiation of heparan sulfate. The GlcNAc transferase reaction product was sensitive to the action of heparitinase I, establishing the identity of the enzyme to be α1,4-GlcNAc transferase. These results altogether indicate that EXTL2/EXTR2 encodes the α1,4-N- acetylhexosaminyltransferase that transfers GalNAc/GlcNAc to the tetrasaccharide representing the common glycosaminoglycan-protein linkage region and that is most likely the critical enzyme that determines and initiates the heparin/heparan sulfate synthesis, separating it from the chondroitin sulfate/dermatan sulfate synthesis.
- リンク情報
- ID情報
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- DOI : 10.1074/jbc.274.20.13933
- ISSN : 0021-9258
- PubMed ID : 10318803
- SCOPUS ID : 0033553525