Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||HOKKAIDO UNIVERSITY|
KIKUCHI Kunimi Hokkaido Univ. Inst. Genet. Med. Prof., 遺伝子病制御研究所, 教授 (20006117)
TANUMA Nobuhiro Hokkaido Univ. Inst. Genet. Med. Inst., 遺伝子病制御研究所, 助手 (40333645)
NAKAMURA Kouji Hokkaido Univ. Inst. Genet. Med. Inst., 遺伝子病制御研究所, 助手 (70281839)
SHIMA Hiroshi Hokkaido Univ. Inst. Genet. Med. Asso. Prof., 遺伝子病制御研究所, 助教授 (10196462)
|Project Period (FY)
1998 – 2001
Completed(Fiscal Year 2001)
|Budget Amount *help
¥12,000,000 (Direct Cost : ¥12,000,000)
Fiscal Year 2001 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2000 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1999 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥6,400,000 (Direct Cost : ¥6,400,000)
|Keywords||protein phosphatase / phosphotyrosine phosphatase / dual specificity phosphatase / PTPε / tautomycetin / cell differentiation / IL-6 / apoptosis / チロシンホスファタ-ゼ / セリンホスファタ-ゼ / 2重基質特異性ホスファタ-ゼ / PTPεC / インヒビター4 / トウトマイシン / 癌化 / 2重特異性ホスファターゼ|
Our results are summarized as follows:
1. Regulation of cytokine signaling by PTPεC
(1) PTPεC strongly suppressed IL-6-induced M1 differentiation in PTPεC activity-dependent manner. This suppression is due to suppression of JAK-activation.
(2) This suppression by PTPεC was observed in STAT-activation through IL6R and IL10R, but not in those via IFNα/βR and IFNγR.
2. Structure and function of a novel dual specificity phosphatase, MKP-7
(1) MKP-7 has Rhodariese domain, catalytic domain, NLS, and NES.
(2) Substrate specificity is in the order ot JNK>p38>>ERK.
(3) MKP-7 is a shuttle protein between cytosol and nucleus.
3. Structure and function of a novel PP1-inhibitor, 1-4
(1) 1-4 strongly inhibits PP1, IC_<50> being 0.2 nM.
(2) 1-4interacts with PP1C on at least three sites.
4. Structure-function relationship of tautomycin and its related compounds
(1) Different moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis.
(2) Tautomycetin is found to be a strong and specific inhibitor for PP1.