O-Linked N-Acetylglucosamine Is Present on the Extracellular Domain of Notch Receptors

被引:142
作者
Matsuura, Aiko [1 ]
Ito, Makiko [1 ]
Sakaidani, Yuta [1 ]
Kondo, Tatsuhiko [1 ]
Murakami, Kosuke [1 ]
Furukawa, Koichi [2 ]
Nadano, Daita [1 ]
Matsuda, Tsukasa [1 ]
Okajima, Tetsuya [1 ,2 ]
机构
[1] Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Dept Appl Mol Biosci, Nagoya, Aichi 4648601, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Biochem 2, Showa Ku, Nagoya, Aichi 4660065, Japan
关键词
D O I
10.1074/jbc.M806202200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rare types of glycosylation often occur in a domain-specific manner and are involved in specific biological processes. In particular, O-fucose glycans are reported to regulate the functions of EGF domain-containing proteins such as Notch receptors. In the course of mass spectrometric analysis of O-glycans displayed on Drosophila Notch receptors expressed in S2 cells, we found an unusual O-linked N-acetylhexosamine (HexNAc) modification which occurs at a site distinct from those of O-fucose and O-glucose glycosylations. Modification site mapping by mass spectrometry and amino acid substitution studies revealed that O-HexNAc modification occurs on a serine or threonine located between the fifth and sixth cysteines within the EGF domain. This modification occurs simultaneously along with other closely positioned O-glycosylations. This modification was determined to be O-beta-GlcNAc by galactosyltransferase labeling and beta-N-acetyl-hexosaminidase digestion experiments and by immunoblotting with a specific antibody. O-GlcNAc modification occurs at multiple sites on Notch epidermal growth factor repeats. O-GlcNAc modification was also found on the extracellular domain of Delta, a ligand for Notch receptors. Although the O-GlcNAc modification is known to regulate a wide range of cellular processes, the list of known modified proteins has previously been limited to intracellular proteins in animals. Thus, the finding of O-GlcNAc modification in extracellular environments predicts a distinct glycosylation process that might be associated with a novel regulatory mechanism for Notch receptor activity.
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页码:35486 / 35495
页数:10
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