学術雑誌論文

学術雑誌論文

text

Journal of Biological Chemistry. 2008, 283(48), p. 33036-33045

N-Glycosylation of Laminin-332 Regulates Its Biological Functions : A NOVEL FUNCTION OF THE BISECTING GlcNAc

American Society for Biochemistry and Molecular Biology

英語

text

2008-11

https://doi.org/10.1074/jbc.M804526200

This research was originally published in the Journal of Biological Chemistry. Yoshinobu Kariya, Rika Kato, Satsuki Itoh, Tomohiko Fukuda, Yukinao Shibukawa, Noriko Sanzen, Kiyotoshi Sekiguchi, Yoshinao Wada, Nana Kawasaki and Jianguo Gu. N-Glycosylation of Laminin-332 Regulates Its Biological Functions : A NOVEL FUNCTION OF THE BISECTING GlcNAc. J. Biol. Chem. 2008; 283: 33036-33045 © the American Society for Biochemistry and Molecular Biology

Laminin-332 (Lm332) is a large heterotrimeric glycoprotein that has been identified as a scattering factor, a regulator of cancer invasion as well as a prominent basement membrane component of the skin. Past studies have identified the functional domains of Lm332 and revealed the relationships between its activities and the processing of its subunits. However, there is little information available concerning the effects of N-glycosylation on Lm332 activities. In some cancer cells, an increase of β1,6-GlcNAc catalyzed by N-acetylglucosaminyltransferase V (GnT-V) is related to the promotion of cancer cell motility. By contrast, bisecting GlcNAc catalyzed by N-acetylglucosaminyltransferase III (GnT-III) suppresses the further processing with branching enzymes, such as GnT-V, and the elongation of N-glycans. To examine the effects of those N-glycosylations to Lm332 on its activities, we purified Lm332s from the conditioned media of GnT-III- and GnT-V-overexpressing MKN45 cells. Lectin blotting and mass spectrometry analyses revealed that N-glycans containing the bisecting GlcNAc and β1,6-GlcNAc structures were strongly expressed on Lm332 purified from GnT-III-overexpressing (GnT-III-Lm332) and GnT-V-overexpressing (GnT-V-Lm332) cells, respectively. Interestingly, the cell adhesion activity of GnT-III-Lm332 was apparently decreased compared with those of control Lm332 and GnT-V-Lm332. In addition, the introduction of bisecting GlcNAc to Lm332 resulted in a decrease in its cell scattering and migration activities. The weakened activities were most likely derived from the impaired α3β1 integrin clustering and resultant focal adhesion formation. Taken together, our results clearly demonstrate for the first time that N-glycosylation may regulate the biological function of Lm332. This finding could introduce a new therapeutic strategy for cancer.

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N-Glycosylation of Laminin-332 Regulates Its Biological Functions : A NOVEL FUNCTION OF THE BISECTING GlcNAc

American Society for Biochemistry and Molecular Biology

英語

2008-11

Journal of Biological Chemistry

283

48

33036

33045

https://doi.org/10.1074/jbc.M804526200

https://hdl.handle.net/11094/71425