| Project/Area Number |
08308035
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TAKEDA Masao Hiroshima University, Faculty of Medicine, Professor, 医学部, 教授 (40030853)
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| Co-Investigator(Kenkyū-buntansha) |
YAKURA Hidetaka Tokyo Metropolitan Institute for Neuroscience, Department of Microbiology and Im, 微生物学・免疫学研究部門, 参事 (60166486)
KASUGA Masato Kobe University, School of Medicine, Professor, 医学部, 教授 (50161047)
MIYAMOTO Eishichi Kumamoto University, School of Medicine, Professor, 医学部, 教授 (50109659)
TAMURA Shinri Tohoku University, Institute of Development, A ging and Cancer, Professor, 加齢医学研究所, 教授 (20124604)
KIKUCHI Kunimi Hokaido University, Reseach Section of Biochemistry Institute of Immunological S, 免疫科学研究所, 教授 (20006117)
日野田 裕治 札幌医科大学, 助教授 (10165128)
久野 高義 神戸大学, 医学部, 教授 (50144564)
渡邊 利雄 東北大学, 加齢医学研究所, 助教授 (60201208)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥18,100,000 (Direct Cost: ¥18,100,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1996: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | Signal transduction / Protein phosphatase / Serine / threonine protein phosphatase / Tyrosine protein phosphatase / Tautomycin / SHPS-1 / SHP-2 / B cell antigen receptor / ノジュラリン / CD45 / 長期増強 / アルツハイマー病 / オカダ酸 |
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| Research Abstract |
(Takeda) Human erythrocyte PP2A (CAB") was phosphorylated in vitro by A-kinase at Ser-60, -75 and -573 of B" without dissociation of B" from CA, and was stimulated in the activity toward P-histones ; (Kikuchi) Activities and amounts of nuclear type I protein phosphatase (PP1) were elevated in human HepG2 and rat AHI3 hepatoma cells compared with primary cultured hepatocytes. The nuclear PP1 activities were more elevated at the (Gl/S transition in hepatoma cells, the extent of the elevation being much less in hepatoma cells than in hepatocytes ; (Kuno) Disruption of the PP2B gene in fission yeast resulted in a drastic chloride ion-sensitive growth defect. High copy of two novel genes pmpl+ and pekl+ suppress this defect. pmpl+ encodes a MAP kinase phosphatase which negatively regulates Pmkl, the third MAP kinase in fission yeast pekl+ encodes a novel MAPKK member, which phosphorylates and activates the Pmkl MAPK ; (Tamura) Protein phosphatase 2Calpha (PP2Calpha) or PP2Cbeta-l expressed
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in COS7 cells suppressed anisomycin- and NaCI-enhanced phosphorylations of p38 coexpressed in the cells. PP2Calpha or PP2Cbeta-l expression also suppressed both basal and stress-enhanced phosphorylations of MKK3b, MKK6b and MKK4 but not those of MKKla. A dominant negative form of PP2Cbeta-l enhanced farther the NaCl-stimulated phosphorylations of MKK3b, MKK4 and MKK6b. These results suggest that PP2C inhibits selectively the SAPK pathways through suppression of MKK3b, MKK4, and MKK6b activities in mammalian cells ; (Miyamoto) l)Protein phosphatases which are responsible for the phosphorylation sites by proline-directed protein kinases were investigated. In this connection, protein phosphatases for phosphorylated tau in neurofibrillary tangles Alzheimer's brain was studied. 2) Decreases in protein phosphatase activities during induction of long-term potentiation in hippocampus was studied ; (Fujiki, ) Inhibitors of PP-l and PP-2A, okadaic acid and microcystin are potent tumor promoters of skin, glandular stomach and liver. However, tautomycin, an inhibitor of PP-1 and PP-2A, did not show any tumor promoting activity in mouse skin and rat glandular stomach. Okadaic acid and microcystin induced tumor necrosis factor-alpha (TNF-alpha) gene expression in their target organs, but tautomycin did not. Effects of tautomycin on JNK activation snd cell cycle regulation are different from those of okadaic acid ; (Kasuga) SHP substrate-l (SHIPS-1) with Ig-like domains in its extracellular region and four YXX(L/ V/I) motifs in its cytoplasmic region was identified. Various mitogens induced tyrosine phosphorylation of SHPS-i and its subsequent association with SAP-2/SHP-2. Thus, SHPS-l may be a direct substrate for both tyrosine kinases and SAP-2/SAP-2 and also be a specific docking protein for SH2 domain-containing PTPases ; (Hinoda) Tyrosine phosphorylation of SHP-2 was involved in the signal transduction pathways by IL-2 stimulation. Since this SHP-2 activation is irrelevant to Less
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