2005 Fiscal Year Final Research Report Summary
The roles of N-glycans in complex formation of integrins and growth factor receptors.
| Project/Area Number |
16570160
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Osaka University |
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Principal Investigator |
GU Jianguo Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40260369)
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| Project Period (FY) |
2004 – 2005
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| Keywords | N-glycan / glycosyltransferase / integrin / growth factor receptor / complex formation |
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| Research Abstract |
Recent studies have shown that growth factor-induced proliferation, cell-cycle progression and differentiation require the adhesion of cells to the ECM, a process that is mediated by integrins. Integrins and growth factor receptors share many common elements in their signaling pathways. In fact, integrins enable growth factor signaling in many cases, since normal growth factor signaling does not occur unless cells are adhered to the ECM or to other cells through integrins. It is well known that a large number of proteins undergo posttranslational modification with corresponding changes in their structures and functions. Among the various posttranslational modification reactions of proteins, glycosylation is the most abundant. A growing body of evidence indicates that the presence of the appropriate oligosaccharide can modulate integrin activation, therefore, it has been proposed that N-glycosylation is essential for functional integrins and complex formation of integrins with growth fa
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ctor receptors. Actually, integrins are major carriers of N-glycans on cell surface. We found that : 1)the overexpression of GnT-III resulted in an inhibition of alpha5beta1 integrin-mediated cell spreading and migration, and the phosphorylation of the focal adhesion kinase ; 2)the beta1 integrin modulated with a bisecting GlcNAc can play important roles in the regulation of neuritogenesis ; 3)the core fucosylation plays an essential role in integrin- and EGFR-mediated functions. The EGF-induced phosphorylation levels of EGFR were substantially blocked in Fut8-null cells, compared with wild-type cells. As described above, modulation of the N-glycans of these receptors could significantly alter their biological functions. Since they contain multiple potential N-linked glycosylation sites, it is essentially important to identify the sites that are occupied by N-glycans, which N-glycans are required for their functions, as well as which N-glycans are participated in the complex formation in the future. Less
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Research Products
(23 results)
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[Journal Article] Fucosylated haptoglobin is a novel marker for pancreatic cancer : A detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation.2006
Author(s)
Okuyama N, Ide Y, Nakano M, Nakagawa T, Yamanaka K, Moriwaki K, Murata K, Ohigashi H, Yokoyama S, Eguchi H, Ishikawa O, Ito T, Kato M, Kasahara A, Kawano S, Gu J, Taniguchi N, Miyoshi E.
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Journal Title
Int.J.Cancer 118
Pages: 2803-2808
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] High expression of N-acetylglucosaminyltransferase V in favorable neuroblastomas : Involvement of its effect on apoptosis.2006
Author(s)
Inamori, K., Gu, J., Ohira, M., Kawasaki, A., Nakamura, Y., Nakagawa, T., Kondo, A., Miyoshi, E., Nakagawara, A., Taniguchi, N.
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Journal Title
FEBS Letters 580
Pages: 627-632
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Demonstration of the expression and the enzymatic activity of N-acetylglucosaminyltransferase IX in the mouse brain.2006
Author(s)
Inamori, K., Mita, S., Gu, J., Mizuno-Horikawa, Y., Miyoshi, E., Dennis, JW., Taniguchi, N.
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Journal Title
Biochim Biophys Acta 1760
Pages: 678-684
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cell-cell interaction-dependent regulation of N-acetylglucosaminyltransferase III and the bisected N-glycans in GE11 epithelial cells : involvement of E-cadherin-mediated cell adhesion.2006
Author(s)
Iijima J, Zhao Y, Isaji T, Kameyama A, Nakaya S, Wang X, Ihara H, Cheng X, Nakagawa T, Miyoshi E, Kondo A, Narimatsu H, Taniguchi N, Gu J.
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Journal Title
J.Biol.Chem. 281
Pages: 13038-13046
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice.2005
Author(s)
Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, Mizuno-Horikawa Y, Nakano M, Asahi M, Takahashi M, Uozumi N, Ihara S, Lee SH, Ikeda Y, Yamaguchi Y, Aze Y, Tomiyama Y, Fujii J, Suzuki K, Kondo A, Shapiro SD, Lopez-Otin C, Kuwaki T, Okabe M, Honke K, Taniguchi N.
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Journal Title
Proc Natl Acad Sci USA. 102
Pages: 15791-15796
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Introduction of bisecting GlcNAc into integrin alpha5beta1 reduces ligand binding and down-regulates cell adhesion and cell migration.2004
Author(s)
Isaji, T., Gu, J., Nishiuchi, R., Zhao, Y., Takahashi, M., Miyoshi, E., Honke, K., Sekiguchi, K., Taniguchi, N.
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Journal Title
J.Biol.Chem. 279
Pages: 19747-19754
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] β1, 4-N-acetylglucosaminyltransferase III Down-regulates Neurite Outgrowth Induced by Co-stimulation of Epidermal Growth Factor and Integrins Through the Ras/ERK Signaling Pathway in PC12 cells.2004
Author(s)
Gu, J., Zhao, Y., Isaji T., Shibukawa, Y., Ihara, H., Takahashi, M., Ikeda, Y., Miyoshi, E., Honke, K., Taniguchi, N.
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Journal Title
Glycobiology 14
Pages: 177-186
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] N-acetylglucosaminyltransferase IX acts on the GlcNAcbeta 1,2-Manalpha 1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan.2004
Author(s)
Inamori, KI., Endo, T., Gu, J., Matsuo, I., Ito, Y., Fujii, S., Iwasaki, H., Narimatsu, H., Miyoshi, E., Honke, K., Taniguchi, N.
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Journal Title
J.Biol.Chem. 279
Pages: 2337-2340
Description
「研究成果報告書概要(欧文)」より
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