2006 Fiscal Year Final Research Report Summary
Regulation of stress-activated protein kinase signaling pathway by protein phosphatase 2C (PP2C)
| Project/Area Number |
14086201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tohoku University |
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Principal Investigator |
KOBAYASHI Takayasu Tohoku University, Institute of Development, Aging and Cancer, Assistant Professor (10221970)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Shinri Tohoku University, Professor (20124604)
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| Project Period (FY) |
2002 – 2006
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| Keywords | protein phosphatase / stress / SAPK |
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| Research Abstract |
(1) PP2Cε precipitates in negative regulation of TAK1 and ASK1
Ectopic expression of PP2Cε in mammalian cells represses the activity of TAK1 and ASK1, two mitogen-activated protein kinase kinase kinases. PP2Cε keeps these kinases in an inactive state in quiescent cells by associating with and dephosphorylating them. PP2Cε associated with TAK1 and ASK1 in quiescent cells, but the association was transiently suppressed in response to treatment of the cells with IL-1 and H_2_O_2, respectively, which activate these respective kinases. On the basis of these results we proposed that PP2Cε regulates TAK1 and ASK1 pathways by a common regulatory mechanism.
(2) PP2Cδ (ILKAP) participates in positive regulation of ASK1
In contrast to PP2Cε, PP2Cδ (ILKAP) acts as a positive regulator of TNF induced SAPK signaling. Transient expression of PP2Cδ (ILKAP) in 293 cells enhanced TNF induced activation of JNK and p38. PP2Cδ (ILKAP) associated with ASK1 and this association was enhanced in response to TNF treatment. These results suggested that PP2Cδ (ILKAP) may dephosphorylate inhibitory phosphorylation site(s) of ASK1.
(3) JNK negatively regulates PP2Cζ
PP2Cζ, a PP2C family member that is enriched in testicular germ cells, is phosphorylated at Ser92 and Thr202/205 by JNK but not by p38 or ERK both in vivo and in vitro. We show that phosphorylation of PP2Cζ at Ser92 but not at Thr202/205 repressed its phosphatase activity.
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Research Products
(34 results)
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[Journal Article] Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase 2Cε.2007
Author(s)
Saito, J., Toriumi, S., Awano. K., Ichijo, H., Sasaki, K., Kobayashi, T., Tamura, S.
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Journal Title
Biochem. J. 405
Pages: 591-596
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Disruption of the mouse protein Ser/Thr phosphatase 2Cβ gene leads to early pre-implantation lethality.2007
Author(s)
Sasaki, M., Ohnishi, M., Tashiro, F., Niwa, H., Suzuki, A., Miyazaki, J., Kobayashi, T., Tamura., S.
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Journal Title
Mech. Dev. 124
Pages: 489-499
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Catalyst-contorolled asymmetric synthesis of fostriecin and 8-epi-fostriecin.2005
Author(s)
Maki, K., Motoki, R., Fujii, K., ^*Kanai, M., Kobayashi, T., Tamura, S. ^*Shibasaki, M.
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Journal Title
J. Am. Chem. Soc. 127
Pages: 17111-17117
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Activation mechanism of c-Jun amino-terminal kinase in the course of neural differentiation of P19 embryonic carcinoma cells.2004
Author(s)
Akiyama, S., Yonezawa, T., Kudo, T., Li, M. G., Wang, H., Ito, M., Yoshioka, K., Ninomiya-Tsuji, J., Matsumoto, K., Kanamaru, R., ^*Tamura, S., ^*Kobayashi, T.
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Journal Title
J. Biol. Chem. 279
Pages: 36616-36620
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Roles of mammalian protein phosphotase 2C family members in regulation of cellular functions.2004
Author(s)
Tamura, S., Li, M. G., Komaki, K., Sasaki, M., ^*Kobayashi, T.
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Journal Title
In TCG Protein Phosphatases, ((Arino, J., & Alexander, D., Eds). Springer-Verlag, Heiderberg. )
Pages: 91-105
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protein phosphatase 2Ca as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.2004
Author(s)
Yoshizaki, T., ^*Maegawa, H., Egawa, K., Ugi, S., Nishio, Y., Imamura, T., Kobayashi, T., Tamura, S., Olefsky, J. M., Kashiwagi, A.
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Journal Title
J. Biol. Chem. 279
Pages: 22715-22726
Description
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[Journal Article] A novel protein phosphatase 2C family member (PP2C) is able to associate with ubiquitin conjugating enzyme 9.2003
Author(s)
Kashiwaba, M., Katsura, K., Ohnishi, M., Sasaki, M., Tanaka, H., Nishimune, Y., ^*Kobayashi, T., ^*Tamura, S.
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Journal Title
FEBS Lett. 538
Pages: 197-202
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Structural and functional characterization of mouse glutamate decarboxylase 67 gene promoter.2003
Author(s)
Kobayashi, T., Ebihara, S., Ishii, K., Kobayashi, T., Nishijima, M., Endo, S., Takaku, A., Sakagami, H., Kondo, H., Tashiro, F., Miyazaki, J. -I., Obata, K., Tamura, S., ^*Yanagawa, Y.
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Journal Title
Biochim. Biophys. Acta 1628
Pages: 156-168
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular cloning of PP2Ch, a novel member of the protein phosphatase 2C family.2003
Author(s)
Komaki, K., Katsura, K., Ohnishi, M., Li, M. G., Sasaki, M., Watanabe, M., Kobayashi, T., ^*Tamura, S.
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Journal Title
Biochim. Biophys. Acta 1630
Pages: 130-137
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of the interleukin-1-induced signaling pathways by a novel member of protein phosphatase 2C family (PP2Ce).2003
Author(s)
Li, M. G., Katsura, K., Nomiyama, H., Komaki, K. I., Ninomiya-Tsuji, J., Matsumoto, K., ^*Kobayashi, T., ^*Tamura, S.
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Journal Title
J. Biol. Chem. 278
Pages: 12013-12021
Description
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[Journal Article] IGF-1 up-regulates K^+ channels via PI3-kinase, PDK1 and SGK1.2002
Author(s)
Gamper, N., Fillon, S., Huber, S. M., Feng, Y., Kobayashi, T., Cohen, P., ^*Lang, F.
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Journal Title
Eur. J. Physiol. 443
Pages: 625-634
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] K^+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK.2002
Author(s)
Gamper, N., Fillon, S., Feng, Y., Friedrich, B., Lang, P. A., Henke, G., Huber, S. M., Kobayashi, T., Cohen, P., ^*Lang, F.
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Journal Title
Eur. J. Physiol. 445
Pages: 60-66
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of stress-activated protein kinase signaling pathways by protein phosphatases.2002
Author(s)
^*Tamura, S., Hanada, M., Ohnishi, M., Katsura, K., Sasaki, M., Kobayashi, T.
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Journal Title
Eur. J. Biochem. 269
Pages: 1060-1066
Description
「研究成果報告書概要(欧文)」より
