Document Detail

N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3beta1 integrin-mediated cell migration.
MedLine Citation:
PMID:  16940045     Owner:  NLM     Status:  MEDLINE    
N-acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of beta1,6-GlcNAc branching of N-glycans, which contributes to metastasis. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulting in the suppression of metastasis. It has long been hypothesized that the suppression of GnT-V product formation by the action of GnT-III would also exist in vivo, which will consequently lead to the inhibition of biological functions of GnT-V. To test this, we draw a comparison among MKN45 cells, which were transfected with GnT-III, GnT-V, or both, respectively. We found that alpha3beta1 integrin-mediated cell migration on laminin 5 was greatly enhanced in the case of GnT-V transfectant. This enhanced cell migration was significantly blocked after the introduction of GnT-III. Consistently, an increase in bisected GlcNAc but a decrease in beta1,6-GlcNAc-branched N-glycans on integrin alpha3 subunit was observed in the double transfectants of GnT-III and GnT-V. Conversely, GnT-III knockdown resulted in increased migration on laminin 5, concomitant with an increase in beta1,6-GlcNAc-branched N-glycans on the alpha3 subunit in CHP134 cells, a human neuroblastoma cell line. Therefore, in this study, the priority of GnT-III for the modification of the alpha3 subunit may be an explanation for why GnT-III inhibits GnT-V-induced cell migration. Taken together, our results demonstrate for the first time that GnT-III and GnT-V can competitively modify the same target glycoprotein and furthermore positively or negatively regulate its biological functions.
Yanyang Zhao; Takatoshi Nakagawa; Satsuki Itoh; Kei-ichiro Inamori; Tomoya Isaji; Yoshinobu Kariya; Akihiro Kondo; Eiji Miyoshi; Kaoru Miyazaki; Nana Kawasaki; Naoyuki Taniguchi; Jianguo Gu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-23     Completed Date:  2006-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32122-30     Citation Subset:  IM    
Departments of Biochemistry and Glycotherapeutics, Osaka University Graduate School of Medicine, B1, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
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MeSH Terms
Cell Line, Tumor
Cell Movement*
Epithelial Cells / physiology
Integrin alpha3beta1 / metabolism*
Integrin alpha5beta1 / metabolism*
Models, Biological
N-Acetylglucosaminyltransferases / antagonists & inhibitors*
RNA, Small Interfering / metabolism
Retroviridae / genetics
Stomach Neoplasms / metabolism,  pathology
Reg. No./Substance:
0/Integrin alpha3beta1; 0/Integrin alpha5beta1; 0/RNA, Small Interfering; EC 2.4.1.-/N-Acetylglucosaminyltransferases; EC,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase

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