2003 Fiscal Year Final Research Report Summary
Studies on integrinα3β1-mediated signaling
| Project/Area Number |
14580697
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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, Biochemistry, Associate Professor, 医学系研究科, 助教授 (40260369)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIGUTI Kiyotoshi Institute for Protein Research, Professor, 蛋白質研究所, 教授 (50187845)
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| Project Period (FY) |
2002 – 2003
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| Keywords | basement membrane / integrin / laminin / phosphotyrosine / matrix metallonroteinase / signal / N-glycan |
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| Research Abstract |
The α3β1 integrin-mediated signaling events triggered by cell adhesion to laminin-10/11(LN-10/11) are quite different from those triggered by adhesion to fibronectin (FN). LN-10/11 preferentially activates Rac, but not Rho, through an α3β1 integrin-dependent pathway involving a p130Cas-CrkII-DOCK18O complex, thereby strongly promoting cell migration through enhanced formation of lamellipodia. On the other hand, the intracellular signaling pathways regulating cell survival focusing on two distinct signaling pathways involving PI 3-kinase/Akt and MEKi/ERK have been investigated. LN-10/11 is more potent than FN in suppressing apoptosis induced by serum deprivations The anti-apoptotic effects of LN-10I11 could be inhibited by the PI 3-kinase inhibitor wortmannin, whereas the anti-apoptotic effects of FN were inhibited by the MEKi inhibitor PD98059. Our results provide clear evidence that different signaling pathways leading to cell survival are activated, on different ECM ligands. Furthermore, remodeling of N-glycans of the integrin could also modulate its ligand binding and integrin-mediated signaling. Since laminins are the major components of the basement membrane of epithelium, our work supports the notion that a function of the basement membrane is to provide distinctive cell survival signals for establishment and maintenance of epithelial tissue.
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[Publications] Noda, K., Miyoshi, E., Gu., J., Gao, C-X., Nakahara, S., Kitada, T., Honke, K., Suzuki, K., Yoshihara, H., Yoshikawa, K., Kawano, K., Tonetti, M., Kasahara, A., Hori M, Hayashi, N., Taniguchi, N.: "Relationship between elevated FX expression and increased production of GDP--fucose, a common donor substrate for fucosylation in human hepatocellular carcinoma and hepatoma celllines."Cancer, Res. 63. 6282-6289 (2003)
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[Publications] Inamori, K., Endo, T., Ide, Y, Fujii, S., Gu., J., Honke, K., Taniguchi, N.: "Molecular Cloning and Characterization of Human GnT-IX, A Novel β1,6-N-Acetylglucosaminyltransferase That Is Specifically Expressed in The Brain."J.Biol.Chem. 278. 43102-43109 (2003)
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[Publications] Kozaki, T., Matsui, Y, Gu., J., Nishiuchi, R., Sugiura, N., Kimata, K., Ozono, K., Yoshikawa, H.Sekiguchi, K.: "Recombinant Expression and Characterization of a Novel Fibronectin Isoform Expressed in Cartilaginous Tissues."J.Biol.Chem. 278. 50546-50553 (2003)
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[Publications] Gu., J., Zhao, Y., Isaji T., Shibukawa, Y, Ihara, H., Takahashi, M., Ikeda, Y, Miyoshi, E., Honke, K., Taniguchi, N.: "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."Glycobiology. 14. 177-186 (2004)
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[Publications] Inamoni, K., Endo, T., Gu.J., Matsuo, I., Ito, Y, Fujii, S., Iwasaki, H., Narimatsu, H., Miyoshi, B., Honke, K., Taniguchi, N.: "N-acetylglucosaminyltransferase IX acts on the GlcNAcbeta 1,2-Manalpha 1-Ser/Thr moiety, forming α 2,6-branched structure in brain 0-mannosyl glvcan"J.biol.Chem. 279. 2337-2340 (2004)
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[Publications] Isaji, T., gu, J., Nishiuchi, R., Zhao, Y, Takahashi, M., Miyoshi, E., Honke, K., Sekiguchi, K., Taniguchi, N.: "Introduction of bisecting GlcNAc into integrin α5β1 reduces ligand binding and down-regulates cell adhesion and cell migration."J.Biol.Chem. 279. 19747-19754 (2004)
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