1999 Fiscal Year Final Research Report Summary
Functions of the stress-signaling kinase SEK1 in mouse immune System and development
| Project/Area Number |
10680599
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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 |
Functional biochemistry
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| Research Institution | The University of Tokyo (Graduate School of Pharmaceutical Sciences) |
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Principal Investigator |
NISHINA Hiroshi The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Associate Professor, 大学院・薬学系研究科, 助教授 (60212122)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Kenji The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Research fellow, 大学院・薬学系研究科, 助手 (30302615)
HOSHINO Shin-ichi The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Research fellow, 大学院・薬学系研究科, 助手 (40219168)
KATADA Toshiaki The University of Tokyo Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Professor, 大学院・薬学系研究科, 教授 (10088859)
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| Project Period (FY) |
1998 – 1999
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| Keywords | signal transduction / stress signal / kinase cascade / liver formation / SEK1 |
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| Research Abstract |
The stress signal kinase SEK1/MKK4 is a direct activator of stress-activated protein kinase (SAPKs ; also called c-Jun-N- terminal kinases, JNKs) in response to a variety of cellular stresses, such as changes in osmolarity, metabolic poisons, DNA damages, heat shock or inflammatory cytokines. We have disrupted the sek1 gene in mice using homologous recombination. Sek1ィイD1-/-ィエD1 embryos displayed severe anemia and died between embryonic day 10.5(E10.5) and E12.5. In the present study, we investigated the functions and properties of SEK1 and its related kinase, SEK2/MKK7. 1. Hematopoiesis and vasculogenesis are normal in sek1ィイD1-/-ィエD1 embryos. However, hepatogenesis and liver formation were severely impaired in the mutant embryos and E11.5 and E12.5 sek1ィイD1-/-ィエD1 embryos had greatly reduced numbers of parenchymal hepatocytes. Sek1ィイD1-/-ィエD1 liver cells underwent massive apoptosis. These results provide the first genetic link between SEK1 and organogenesis in mammals and indicate that SEKI provides a crucial and specific survival signal for hepatocytes. 2. We disrupted the sek2 gene in mouse embryonic stem (ES) cells using the Cre-10xP system. Sek2ィイD1-/-ィエD1 ES cells did not grow and died, Thus. SEK2 is a crucial survial molecule for ES cells. 3. We prepared monoclonal antibodies to mouse fetal liver. One of them, anti-Liv1 specifically recognized hepatocytes in wild-type embryos, but not in sek1ィイD1-/-ィエD1 embryos. These results indicate that SEK1 regulates Liv1 expression and fetal liver development.
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Research Products
(13 results)
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[Publications] H. Yoshida, H. Nishina, H. Takimoto, L. E. M. Marengere, A. C. Wakeham, D. Bouchard, Y. Y. Kong, T. Ohteki A. Shahinian, M. Bachmann, P. S. Ohashi J. M. Penninger, G. R. Crabtree, and T. W. Mak.: "The Transcription Factor NF-ATc-1 Regulates Lymphocyte Proliferation and Th2 Cytokine Production"Immunity. 8. 115-124 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] K. D. Fischer, Y. Y. Kong, H. Nishina, K. Tedford, L. Marengere, I. Kozieradzki, T. Sasaki, M. Starr. G. Chan, S. Gardener, M. P. Nghiem, D. Bouchard, M. Barbacid, A. Bernstein, and J. M. Penninger: "Vav is a regulator of cytoskeletal reorganization mediated by the T-cell receptor."Current Biology. 8. 554-562 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] H. Nishina, C. Vaz, P. Billia, M. Nghiem, T. Sasaki, J. L. De la Pompa, K. Furlonger, C. Paige, C. Hui, K. D. Fischer, H. Kishimoto, T. Iwatsubo, T. Katada, J. R. Woodgett, J. M. Penninger: "Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4."Development. 126. 505-516 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] K. Bachmaier, C. Krawczyk, I. Kozieradzki, Y. Y. Kong, T. Sasaki, A. Oliveira-dos-Santos, S. Mariathasan, D. Bouchard, A. Wakeham, A. Itie, J. Le, P. Ohashi, I. Sarosi, I., H. Nishina, S. Lipkowitz, and J. M. Penninger: "Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cb1-b"Nature. 403. 211-216 (2000)
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「研究成果報告書概要(欧文)」より
