2001 Fiscal Year Final Research Report Summary
Role of paxillin isoforms and their tyrosine phosphorylation in cell migration.
| Project/Area Number |
10480199
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 BIOSCIENCE INSTITUTE(OBI) |
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Principal Investigator |
SABE Hisataka OBI,FIRST DEPARTMENT,HEAD, 第1研究部, 研究部長 (40187282)
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| Co-Investigator(Kenkyū-buntansha) |
MAZAKI Yuichi OBI, FIRST DEPARTMENT, RESERCH ASSOSIATE, 第1研究部, 研究員 (60311304)
YANO Hajime OBI, FIRST DEPARTMENT, RESERCH ASSOSIATE, 第1研究部, 研究員 (00284414)
HASHIMOTO Sigeru OBI, FIRST DEPARTMENT, RESERCH ASSOSIATE, 第1研究部, 研究員 (50311303)
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| Project Period (FY) |
1998 – 1999
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| Keywords | paxillin / lyrosine phosphorylation / p130Cas / cell motile activity / ARFGAP / membrane trafficing |
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| Research Abstract |
Temporal and spatial regulation of actin-based cytoskeletal organization and focal adhesion formation play an essential role in cell migration. We found that tyrosine phosphorylation of paxillin and pi3OCas was a prominent event upon integrin activation during epithelial-mesenchymal transdifferentiation and cell migration. Tyrosine phosphorylation of p130^<Cas> has been demonstrated to facilitate cell migration. We showed that tyrosine phosphorylation of paxillin cc acts to reduce haptotactic cell migration as well as transcellular invasive activities in several different experimental cell systems, whereas tyrosine phosphorylation of p130^<Cas> exerts opposing effects to those of paxillin
a. Each of the phosphorylation-null mutant acted as dominant-negatives for each phenotype. Moreover, we found that overexpression of paxillin a reduced the cell saturation density of NMuMG cells while overexpression of pi30^<Cas> increased it. These effects also seemed to be dependent on the tyrosine phosphorylation events. Cell growth rates and morphologies at growing phases were not significantly altered, nor were cells transformed. Addition of epidermal growth factor increased saturation density of the paxillin α-overexpressing cells, while no further increment was observed in p130^<Cas>-overexpressing cells. We propose that tyrosine phosphorylation of paxillin a and p130^<Cas> exert opposing effects on several integrin-mediated cellular events, possibly through different signaling pathways. We also found that paxillin binds to several ARFGAPs. ARFGAPs are regulators of intracellular membrane trafficking. We currently analysing role of paxillin from aspects of its tyrosine phosphorylation and its interaction with ARFGAPs, in regulation of cell migratory activity.
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[Publications] Mazaki, Y., Uchida, H., Hino, S., Hashimoto, S., Sabe, H.: "Paxillin isoforms in mice : lack of the γ isoform, and developmentally specific β isoform expression"J.Biol.Chem.. 273・35. 22435-22441 (1998)
Description
「研究成果報告書概要(和文)」より
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[Publications] Takahashi, N., Seko, Y., Norii, E., Tobe, K., Kadowaki, T., Sabe, H., Yazaki, Y.: "Vascular endothelial growth factor (VEGF) induces activation and subcellular translocation of focal adhesion kinase (pp125FAK) in cultured rat cardiac myocytes"Circ.Res.. 84・10. 1194-2202 (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hiiragi, T., Sasaki, H., Nagafuchi, A., Sabe, H., Shen, S.C., Matsuki, M., Yamanishi, K., Tsukita, Sh.: "T ransglutaminase type 1 and its cross-linking activity are concentrated at adherens junctions in simple epithelial cells"J.Biol.Chem.. 274・48. 34148-34154 (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Seko, Y., Takahashi, N., Sabe, H., Tobe, K., Kadowaki, T., Nagai, R.: "Hypoxia induces activation and subcellular translocation of focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes"Biophy.Biochem.Res.Com.. 262・1. 290-296 (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Takahashi, N., Seko, Y., Norii, E., Tobe, K., Kadowaki, T., Sabe, H., and Yazaki, Y.: "Vascular endothelial growth factor (VEGF) induces activation and subcellular translocation of focal adhesion kinase (pp125FAK) in cultured rat cardiac myocytes."Cird. Res.. 84(10). 1194-2202 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hiiragi, T., Sasaki, H., Nagafuchi, A., Sabe, H., Shen, S.C., Matsuki, M, Yamanishi, K., and Tsukita, Sh.: "T ransglutaminase type 1 and its cross-linking activity are concentrated at adherens junctions in simple epithelial cells."J. Biol. Chem.. 274(48). 34148-34154 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Seko, Y., Takahashi, N., Sabe, H., Tobe, K., Kadowaki, T., and Nagai, R.: "Hypoxia induces activation and subcellular translocation of focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes"Biophy. Biochem. Res. Com.. 262(1). 290-296 (1999)
Description
「研究成果報告書概要(欧文)」より
