The Relationship between the Branch-Forming Glycosyltransferases and Cell Surface Sugar Chain Structures
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- 作者：Shinji Takamatsu ; Noboru Inoue ; Toshiyuki Katsumata ; Katsumi Nakamura ; Yasuhisa Fujibayashi ; and Makoto Takeuchi
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：April 26, 2005
- 年：2005
- 卷：44
- 期：16
- 页码：6343 - 6349
- 全文大小：160K
- 年卷期：v.44,no.16(April 26, 2005)
- ISSN：1520-4995
文摘
Many recombinant proteins developed or under development for clinical use are glycoproteins,and trials aimed at improving their bioactivity or pharmacokinetics in vivo by altering specific glycanstructures are ongoing. For pharmaceuticals of glycoproteins, it is important to characterize and, if possible,control the glycosylation profile. However, the mechanism responsible for the regulation of sugar chainstructures found on naturally occurring glycoproteins is still unclear. To clarify the relationship betweenglycosyltransferases and sugar chain branch structure, we estimated six glycosyltransferases' activities(N-acetylglucosaminyltransferase (GlcNAcTase)-I, -II, -III, -IV, -V, and 
-1,4-galactosyltransferase (GalT))which control the branch formation on asparagine (Asn)-linked sugar chains in 18 human cancer celllines derived from several tissues. To visualize the balance of glycosyltransferase activity associated witheach cell line, we expressed the relative glycosyltransferase activity in comparison to the average activityamong the cell lines. These cell lines were classified into five groups according to their relativeglycosyltransferase balance and were termed GlcNAcTase-I/-II, GlcNAcTase-III, GlcNAcTase-IV,GlcNAcTase-V, and GalT. We also characterized the structures of Asn-linked sugar chains on the cellsurface of representative cell lines of each group. The branching structure of cell surface sugar chainsroughly corresponded to the glycosyltransferase balance. This finding suggests that, for the sugar chainstructure remodeling of glycoproteins, attention should be focused on the glycosyltransferase balance ofhost cells before introducing exogenous glycosyltransferases or down-regulating the activity of intrinsicglycosyltransferases.
-1,4-galactosyltransferase (GalT))which control the branch formation on asparagine (Asn)-linked sugar chains in 18 human cancer celllines derived from several tissues. To visualize the balance of glycosyltransferase activity associated witheach cell line, we expressed the relative glycosyltransferase activity in comparison to the average activityamong the cell lines. These cell lines were classified into five groups according to their relativeglycosyltransferase balance and were termed GlcNAcTase-I/-II, GlcNAcTase-III, GlcNAcTase-IV,GlcNAcTase-V, and GalT. We also characterized the structures of Asn-linked sugar chains on the cellsurface of representative cell lines of each group. The branching structure of cell surface sugar chainsroughly corresponded to the glycosyltransferase balance. This finding suggests that, for the sugar chainstructure remodeling of glycoproteins, attention should be focused on the glycosyltransferase balance ofhost cells before introducing exogenous glycosyltransferases or down-regulating the activity of intrinsicglycosyltransferases.