Molecular mechanisms and their significance of protein phosphatase families which control the network-system of signal transduction
控制信号转导网络系统的蛋白磷酸酶家族的分子机制及其意义
基本信息
- 批准号:14380299
- 负责人:
- 金额:$ 9.54万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1.Using tautomycetin, a novel inhibitor of PP1, we found that PP1 activates Raf-1, resulting in activation of the ERK pathway.2.Expression of C-terminal region-deleted mutant of NIPP1 (NIPP-1-ΔC) induced arrest of the cell cycle and apoptosis. In experiments with a reporter gene, NIPP1-ΔC suppressed splicing of pre-mRNA and decreased level of matured mRNA.3.The PP1α-depleted HeLa cells rounded up and showed increased cell death, indicating that PP1α is essential for cell proliferation.4.Scid and nude mice inoculated with PTPεC-expresser-M1 cells (M1εC) showed significantly prolonged survival time compared with parent M 1 cells.5.Serine-446 in the C-terminal stretch of MKP-7, a novel JNK phosphatase, can be phosphorylated by activated ERK. This phosphorylation stabilized MKP-7 from ubiquitine-dependent degradation. These results strongly suggest that activation of the ERK pathway blocks JNK activation through stabilization of MKP-7 by phosphorylation.6.Forced expression of a novel DSP,LDP-3, in COS-7 cells rathor enhanced activation of JNK and p38.These results demonstrate crucial involvement of protein phosphatases in signal transduction under various conditions including cell proliferation, the cell cycle, cancer, apoptosis, and stress.
1.利用PP 1的新型抑制剂互变霉素,发现PP 1可激活Raf-1,从而激活ERK通路。2. NIPP-1 C端缺失突变体(NIPP-1-ΔC)的表达可诱导细胞周期阻滞和凋亡。在使用报告基因的实验中,NIPP 1-ΔC抑制了前mRNA的剪接,并降低了成熟mRNA的水平。4.Scid和裸小鼠接种PTPε C表达细胞M1(M1εC)后的存活时间较亲本M1细胞明显延长。一种新的JNK磷酸酶MKP-7的末端延伸可以被活化的ERK磷酸化。这种磷酸化稳定了MKP-7,使其免于泛素依赖性降解。这些结果有力地表明,ERK通路的激活通过磷酸化稳定MKP-7来阻断JNK的激活。6.在COS-7细胞中强制表达一种新的DSP,LDP-3,或增强JNK和p38的激活。这些结果表明蛋白磷酸酶在各种条件下的信号转导中起重要作用,包括细胞增殖、细胞周期、癌症、凋亡和应激。
项目成果
期刊论文数量(29)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Analysis of isoform specific function of PP1 catalytic subunits in mammalian cells using siRNA.
使用 siRNA 分析哺乳动物细胞中 PP1 催化亚基的亚型特异性功能。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Ohashi S;Sakashita G;Ban R;Nagasawa M;Matsuzaki H;Murata Y;Taniguchi H;Shima H;Furukawa K;Urano T.;Shinya Mitsuhashi;Chikako Fukukawa;Kentaro Takagaki;Tadashi Okada
- 通讯作者:Tadashi Okada
Horiguchi Takashi: "Transient forebrain ischemia induces expression of serine/threonine protein phosphatase 1 mRNA in the vulnerable regions of gerbil brain"Neuroscience Lett.. 325(2). 115-118 (2002)
Horiguchi Takashi:“短暂的前脑缺血诱导沙鼠大脑脆弱区域丝氨酸/苏氨酸蛋白磷酸酶 1 mRNA 的表达”《神经科学通讯》325(2)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Tanuma, Nobuhiro: "Reduced tumorigenicity of murine leukemia cells expressing protein tyrosine phosphatase, PTPεC"Oncogene. (印刷中). (2003)
Tanuma,Nobuhiro:“表达蛋白酪氨酸磷酸酶 PTPεC 的小鼠白血病细胞的致瘤性降低”Oncogene(2003 年出版)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sagara, Junji: "Scapinin a novel protein inhibitor of protein phosphatase-1 associated with the nuclear nonchromatin structure"J.Biol.Chem.. 276(46). 45611-45619 (2003)
Sagara,Junji:“Scapinin 是与核非染色质结构相关的蛋白磷酸酶 1 的新型蛋白抑制剂”J.Biol.Chem.. 276(46)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Reduced Brcal protein expression in 2-amino 1-methyl 1-6 phenylimidazo [4,5-b]pyridine-induced rat mammary carcinomas
2-氨基 1-甲基 1-6 苯基咪唑[4,5-b]吡啶诱导的大鼠乳腺癌中 Brcal 蛋白表达降低
- DOI:
- 发表时间:2002
- 期刊:
- 影响因子:0
- 作者:Okochi;Eriko
- 通讯作者:Eriko
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KIKUCHI Kunimi其他文献
KIKUCHI Kunimi的其他文献
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{{ truncateString('KIKUCHI Kunimi', 18)}}的其他基金
Studies on control mechanism of protein phosphatases ds a network system of information
信息网络系统中蛋白磷酸酶调控机制的研究
- 批准号:
10480162 - 财政年份:1998
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies of protein phophatases on immune response in normal and autoimmune disease mice.
蛋白磷酸酶对正常和自身免疫性疾病小鼠免疫反应的研究。
- 批准号:
04454164 - 财政年份:1992
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Analysis of Signal Transduction in Immunocompetent Cells by Protein Phosphatase and its Application for Autoimmune Disease
蛋白磷酸酶在免疫活性细胞中的信号转导分析及其在自身免疫性疾病中的应用
- 批准号:
02454152 - 财政年份:1990
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)