The Tumor Suppressor EXT-like Gene EXTL2 Encodes an α1, 4-N-Acetylhexosaminyltransferase That TransfersN-Acetylgalactosamine and N-Acetylglucosamine to the Common Glycosaminoglycan-Protein Linkage…
By H. Kitagawa, H. Shimakawa, K. Sugahara. 1999
We previously demonstrated a unique α-N-acetylgalactosaminyltransferase that transferredN-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 geneEXTL2/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-[3H]GalNAc to various acceptor substrates including GlcAβ1–3Galβ1–3Galβ1–4Xylβ1-O-Ser. Interestingly, the enzyme also catalyzed the transfer ofN-acetylglucosamine (GlcNAc) from UDP-[3H]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 thatEXTL2/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.
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
Citations in the corpus
- The exostosin family: proteins with many functions. (2014, unknown): “1) this activity is weak and has been detected only with a synthetic linkage-region analog as substrate but not with the authentic linkage tetrasacccharide substrate (Kitagawa et al., 1999).”
- Organization of Golgi Glycosyltransferases in Membranes: Complexity via Complexes (2004, background): “…1999 a1,3GalT QKDWWkFPS|Wa Cho and Cummings, 1997; Cho, Yeh, and Cummings, 1997 GM2 synthase GLLkYASTRDAa Jaskiewicz et al., 1996 EXT2 nd Lind et al., 1998 EXTL2 nd Kitagawa, Shimakawa, and Sugahara, 1999 a k denotes the major cleavage site; |, a minor cleavage site(s); the TMD is underlined.”