期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 18, 页码 11873-11881出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M807660200
关键词
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资金
- Core Research for Evolutional Science and Technology
- Japan Science and Technology Agency
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science
- Takeda Science Foundation, Japan
Recently we reported that N-glycans on the beta-propeller domain of the integrin alpha 5 subunit (S-3,4,5) are essential for alpha 5 beta 1 heterodimerization, expression, and cell adhesion. Herein to further investigate which N-glycosylation site is the most important for the biological function and regulation, we characterized the S-3,4,5 mutants in detail. We found that site-4 is a key site that can be specifically modified by N-acetylglucosaminyltransferase III (GnT-III). The introduction of bisecting GlcNAc into the S-3,4,5 mutant catalyzed by GnT-III decreased cell adhesion and migration on fibronectin, whereas overexpression of N-acetylglucosaminyltransferase V (GnT-V) promoted cell migration. The phenomenon is similar to previous observations that the functions of the wild-type alpha 5 subunit were positively and negatively regulated by GnT-V and GnT-III, respectively, suggesting that the alpha 5 subunit could be duplicated by the S-3,4,5 mutant. Interestingly GnT-III specifically modified the S-4,5 mutant but not the S-3,5 mutant. This result was confirmed by erythroagglutinating phytohemagglutinin lectin blot analysis. The reduction in cell adhesion was consistently observed in the S-4,5 mutant but not in the S-3,5 mutant cells. Furthermore mutation of site-4 alone resulted in a substantial decrease in erythroagglutinating phytohemagglutinin lectin staining and suppression of cell spread induced by GnT-III compared with that of either the site-3 single mutant or wild-type alpha 5. These results, taken together, strongly suggest that N-glycosylation of site-4 on the alpha 5 subunit is the most important site for its biological functions. To our knowledge, this is the first demonstration that site-specific modification of N-glycans by a glycosyltransferase results in functional regulation.
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