| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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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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