2003 Fiscal Year Final Research Report Summary
Signal transduction by MAPK cascade scaffold proteins
| Project/Area Number |
13680723
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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 | Kitasato University |
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Principal Investigator |
ITO Michihiko Kitasato University, School of Science, Lecturer, 理学部, 講師 (90240994)
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| Project Period (FY) |
2001 – 2003
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| Keywords | JNK / JSAP1 / JNKBP1 / MAPKinase / NF-kB / MAPK cascade / scaffold protein / cross-talk |
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| Research Abstract |
In mammalian cells, it remains uncertain how the specificity and efficiency of distinct mitogen activated protein kinase (MAPK) cascade signaling modules are regulated, and how a cross-talk between the MAPK and other types of signaling cascade that may play a role on growth, survival, differentiation, or cell death, is done. Key molecules to answer these problems may be scaffold proteins that tether their signaling modules. Previously we isolated and characterized JSAP1 and JNKBP1, which may fuction as scaffold proteins of JNK(MAPK) cascades by organizing the formation of the cascade members into complexes and facilitating JNK activation. In this study, we investigated how these scaffold proteins regulate NF-kB signaling by MAPK kinase kinases. Overexpression of MEKK1 (MAPKKK) into 293T cells activated NF-kB, which was repressed by coexpression of JSAP1 or the other JSAP family member JSAP2. Similarly coexpression of JNKBP1 regulated NF-kB signaling by MEKK1 or TAK1 (MAPKKK). Furthermore, we ascertained the binding between the scaffold proteins and MAPKKKs in 293T cells. These results suggest that the scaffold proteins JSAP1/2 and JNKBP1 may regulate both JNK and NF-kB signaling by interacting with MAPKKKs.
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[Publications] Akechi, M., Ito, M., Uemura, K., Takamatsu, N., Yamashita, S., Uchiyama, K., Shiba, T.: "Expression of JNK scaffold protein JSAP1 in the mouse nervous system."Neurosci.Res.. 39. 391-400 (2001)
Description
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