1996 Fiscal Year Final Research Report Summary
Molecular mechanisms for cell cycle control in the immune system
| Project/Area Number |
07457084
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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 |
Immunology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MINATO Nagahiro Kyoto Univ.Dept.of Immunol.Prof., 医学研究科, 教授 (40137716)
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| Co-Investigator(Kenkyū-buntansha) |
IWAI Kazuhiro Kyoto Univ.Dept.of Immunol.Assist.Prof., 医学研究科, 助手 (60252459)
HATTORI Masakazu Kyoto Univ.Dept.of Immunol.Assist.Prof., 医学研究科, 助手 (40211479)
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| Project Period (FY) |
1995 – 1996
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| Keywords | lymphocutes / small G protein / Rap1 / GTPase activating protein / cell cycle / baculovirus / proliferation / chusmosomal mapping |
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| Research Abstract |
We have molecularly cloned a new gene, Sipa-1, transcriptionally activated in the lymphocytes by mitogenic stimulations. Sipa-1 gene is highly conserved between mouse and human and predominantly expressed in the normal lymphoid tissues of both species. Sipa-1 gene encodes a 130kDa (p130) cytoplasmic protein with SH3-binding, Rapl GAP,PEST,and leucine zipper/coiled coil domains. Baculovirally expressed p130 exhibits a specific GTPase-activating activity (GAP) against a Ras-family small G protein, Rap-1. Overexpression of a truncated Sipa-1 cDNA in NIH3T3 apparently disturbed the entry into the cell cycle in the G0-arrested NIH3T3 following mitogenic stimulation suggesting that the protein is critically involved in the entry into and exit from cell cycle via regulation of Rap-1 GTPase activity. Genomic mapping indicated that Sipa-1 locus is located at the centromeric region of chromosome 19 in mouse and at the centromeric neighborhood of CCND (cyclin D1) at 11q13.3 in human. So far only one RaplGAP (GAP3) has been identified, which was predominantly expressed in the nervous tissues, and the present Sipa-1 is the second species of Rap1GAP preferentially exxpressed in the immune system. Comparative functional analysis of these RaplGAPs in distinct tissues is in progress.
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[Publications] Nishimura, H., Agata, Y., Kawasaki, A., Sato, M., Imamura, S., Minato, N., Yagita, H., Nakano, T., and Honjo, T.: "Developmentally regulated expression of the PD-1 Protein on the surface of double negative (CD4-CD8) thymocytes." Internatl.Immunol. 8. 773-780 (1995)
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[Publications] Sugie, T., Kubota, H., Sato, M., Nakamura, E., Imamura, M., and Minato, N.: "NK1+CD4-CD8-ab T cells in the peritoneal cavity : Specific T cell receptor-mediated cytotoxicity and selective interferon g production against B-cell leukemia and myeloma cells." J.Immunol. 157. 3925-3935 (1996)
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[Publications] Wada, Y., Kubota, H., Maeda, M., Taniwaki, M., Hattori, M., Imamura, S., Iwai, K., and Minato, N: "Mitogen-inducible SPA-1 is mapped at the conserved syntenic groups of the chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human." Genomics. 39. 66-73 (1997)
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[Publications] Nakamura, E., Kubota, H., Sato, M., Sugie, T., Yoshida, O., and Minato, N.: "Involvement of NK1+CD4-CD8- abT cells and endogenous interleukin 4 in non-MHC restricted rejection of embryonal carcinoma in genetically resistant mice" J.Immunol. (in the press).
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