Intracellular transport and molecular chaperone
| Project/Area Number |
15390087
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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 |
General medical chemistry
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| Research Institution | Chiba University |
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Principal Investigator |
AOE Tomohiko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (90311612)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOZUKA Norihiro Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 助手 (80261907)
青野 光夫 千葉大学, 医学部附属病院, 助手 (40292693)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | endoplasmic reticulum / ER stress / KDEL receptor / Golgi / 小胞体ストッレス |
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| Research Abstract |
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) evokes the ER stress response. The resultant outcomes are cytoprotective, but also pro-apoptotic. ER chaperones and misfolded proteins exit to the secretory pathway and are retrieved to the ER, during which process the KDEL receptor plays a significant role. Using an expression of a mutant KDEL receptor that lacks the ability for ligand recognition, we show that the impairment of retrieval by the KDEL receptor led to a mis-sorting of BiP, an ER chaperone that has a retrieval signal from the early secretory pathway, which induced intense ER stress response and an increase in susceptibility to ER stress in HeLa cells. Furthermore, we show that the ER stress response accompanied the activation of p38 MAP kinases and c-Jun amino-terminal kinases (JNKs) and that the expression of the mutant KDEL receptor suppressed the activation of p38 and JNK1 not JNK2. The effect of the expression of the mutant KDEL receptor was consistent with the effect of a specific inhibitor for p38 MAP kinases, since the inhibitor sensitized HeLa cells to ER stress. We also found that the activation of the KDEL receptor by the ligand induced the phosphorylation of p38 MAP kinases. These results indicate that the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signalling, which may affect the outcomes of the mammalian ER stress response.
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004
Author(s)
Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozouka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T
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Journal Title
Mol Cell Biol. Sep:24(18)
Pages: 8007-17
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004
Author(s)
Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozuka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T.
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Journal Title
Mol Cell Biol. Sep;24(18)
Pages: 8007-8017
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004
Author(s)
Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozuka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T.
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Journal Title
Mol Cell Biol. 24
Pages: 8007-8017
Related Report
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[Journal Article] The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades.2003
Author(s)
Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.
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Journal Title
J. Biol. Chem. 278(36)
Pages: 766-72
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades.2003
Author(s)
Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.
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Journal Title
J.Biol.Chem. 278(36)
Pages: 766-772
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.: "The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades."J Biol Chem.. 278. 34525-32 (2003)
