1999 Fiscal Year Final Research Report Summary
COMPARISON OF FUNCTION OF RAS FAMILY MOLECULES
| Project/Area Number |
10680666
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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 | Tokyo Institute of Technology |
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Principal Investigator |
KOIDE Hiroshi FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, ASSISTANT PROFESSOR, 生命理工学部, 寄附講座教員 (70260536)
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| Co-Investigator(Kenkyū-buntansha) |
KAZIRO Yoshito FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, PROFESSOR, 生命理工学部, 寄附講座客員教授 (90012690)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Oncogene / Protein / Molecular Biology / biochemistry / Signal Transduction / GTP-binding protein |
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| Research Abstract |
Ras family is a subfamily of low molecular weight GTP-binding protein and consists of Ras, R-Ras, Ral and Rap. To compare the biological roles of two highly homologous proteins, Ras and R-Ras, IL-3-dependent hematopoietic BaF3 cells and C2C12 myoblasts were utilized. R-Ras, as well as Ras, was found to suppress apoptosis of BaF3 cells upon IL-3 withdrawal. The difference between the two molecules was that activation of Ras alone was enough to inhibit apoptosis, while R-Ras required IGF-1. Further studies. revealed that the observed difference was due to the lack of ERK-activating activity in R-Ras. In the case of C2C12 cells, activation of Ras and R-Ras resulted in different phenotypes. R-Ras promoted differentiation of C2C12 cells, whereas Ras inhibited it. On the other hand, Ras was found to be involved in chemotaxis of C2C12 cells by FGF, HGF and IGF-1, while involvement of R-Ras in the chemotaxis was unlikely since activation of R-Ras was not induced by the three growth factors. Thus, the present study show that Ras and R-Ras play a similar role in survival of hematopoietic cells, but distinct roles in myogenesis.
The relation between Ras and Ral was also examined. Since RalGEF is a Ras effector, existence of the Ras > RalGEF > Ral pathway has been indicated. To examine a role of Ral in Ras-induced cellular transformation, effect of expression of Ral mutants on Ras-dependent anchorage-independent growth was investigated using human fibrosarcoma HT1080 cells. As a result, it was suggested that Ral is involved in Ras-induced anchorage-independent growth of HT1080 cells and that Ral may modulate the anchorage-independent growth through regulation of the amount of a cell cycle inhibitor, p27Kip1.
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Research Products
(6 results)
