Molecular mechanisms of STAT3 activation and their therapeutic applications
| Project/Area Number |
18390017
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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 |
Biological pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
MATSUDA Tadashi Hokkaido University, Grad. Sch. Pharm. Sci., Professor (20212219)
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| Co-Investigator(Kenkyū-buntansha) |
OHBAYASHI Norihiko Hokkaido University, Grad. Sch. Pharm. Sci., Assistant Professor (40421979)
SEKINE Yuichi Hokkaido University, Grad. Sch. Pharm. Sci., Res. Assi. (20396295)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,890,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2007: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Immunology / Signal transduction / cancer / Drug development / cytokine / STAT3 / autoimmune diseases / 創薬 |
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| Research Abstract |
STAT3 protein is mainly activated by IL-6 family of cytokines, epidermal growth factor, and leptin. Like other members of STAT family, STAT3 is tyrosine-phosphorylated by Jak kinases, then forms a dimer and translocates into the nucleus to activate target genes. It has been shown that the activated STAT3 alone can mediate cellular transformation. We cloned IL-6 as B cell stimularory factor 2 in 1986, and found its multiple functions and the relationship with several autoimmune diseases and cancers. After these outstanding works, we have continued the research concerning the mechanisms of IL-6 signal transduction. Especially, we have focused on STAT3 molecule in the IL-6/STAT3-mediated signaling pathway and reported several molecules, which regulate STAT3 positively or negatively. We also identified novel STAT3 binding proteins by using yeast two-hybrid system. Among them, one is ZIPK, a Ser/Thr kinase which phosphorylates STAT3 directly. We have also reported other STAT3 regulators, STAP-2, Daxx and LMW-DSP2 (DUSP22). In our research, we expect that STAT3 regulators, which directly interact with STAT3, may have critical roles in the regulation of STAT3 activation. More detailed understanding of interactions between these molecules and STAT3 is therefore important as new information may provide novel therapeutic approaches for the pathological conditions, including cancer and autoimmune diseases.
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Report
(3 results)
Research Products
(48 results)
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[Journal Article] Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence.2007
Author(s)
Shide, K., Shimoda, K., Kamezaki, K., Kakumitsu, H., Kurnamo, T. Numata, A., Ishikawa, F., Takenaka, K., Yamamoto, K., Matsuda, T., and M. Harada
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Journal Title
Leuk. Res 31
Pages: 1085-1092
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] DUSP22/LMW-DSP2 regulates estrogen receptor a-mediated signaling through dephosphorylation of Ser-118.2007
Author(s)
Sekine, Y., Ikeda, 0., Hayakawa, Y., Tsuji, S. Imoto, S., Aoki, N., Sugiyama, K., and T. Matsuda
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Journal Title
Oncogene 26
Pages: 6038-6049
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells.2007
Author(s)
Ikeda, 0., Sekine, Y., Kakisaka, M., Tsuji, S., Muromoto, R., Ohbayashi, N., Oritani, K., Yoshimura A., and T. Matsuda
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Journal Title
Biochem. Biophys. Res. Commun 358
Pages: 931-937
NAID
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] STAP-2 regulates integrin-mediated T-cell adhesion through protein degradation of FAK.2007
Author(s)
Sekine, Y., Tsuji, S., Ikeda, 0., Sugiyma, K., Oritani, K., Shimoda, K., Muromoto, R., Ohbayashi, N., Yoshimura, A., and T. Matsuda
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Journal Title
J. Immunol 179
Pages: 2397-2407
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice.2007
Author(s)
Shimoda, H. K., Yamamoto, M., Shide, K., Kamezaki, K., Matsuda, T., Ogawa, K., Harada, M., and K. Shimoda
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Journal Title
Am. J. Hematol 82
Pages: 802-806
Description
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[Journal Article] Modulation of Toll-like receptor 4 signaling by a novel adaptor protein STAP-2 in macrophages.2006
Author(s)
Sekine, Y., T. Yumioka, T. Yamamoto, R. Muromoto, S. Imoto, K. Sugiyma, K. Oritani, K. Shimoda, M. Minoguchi, S. Akira., A.Yoshimura and T. Matsuda
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Journal Title
J. Immunol 176
Pages: 380-389
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation of integrin-mediated T-cell adhesion by STAP-2.2007
Author(s)
Sekine, Y., Tsuji, S., Ikeda, 0., Kakisaka, M, Sugiyama, K., and T. Matsuda.
Organizer
The 128th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama (Toyama University)
Year and Date
2007-03-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] LMW-DSP2/DUSP22 regulates STAT3 activation.2007
Author(s)
Matsuda, T., Tsuji, S., Sugiyama K., and Y. Sekine.
Organizer
The 128th Annual Meeting of the Pharmaceutical Society of Japan
Place of Presentation
Toyama (Toyama University)
Year and Date
2007-03-30
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] STAP-2 is involved in the LMP1-mediated signaling.2006
Author(s)
keda, 0., Sekine, Y., Tsuji, S., Ysui, A., Sugiyamai, K., Yoshimura A., and T. Matsuda.
Organizer
The 36th Annual Meeting of the Japanese Society for Immunology
Place of Presentation
Osaka (Osaka International Conference Center)
Year and Date
2006-12-12
Description
「研究成果報告書概要(欧文)」より
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