Analysis of the Function of a Novel Class of Mammalian Phospholipase C, PLCε

一类新型哺乳动物磷脂酶 C (PLCε) 的功能分析

基本信息

  • 批准号:
    13470022
  • 负责人:
  • 金额:
    $ 9.34万
  • 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:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

We have clarified the regulation mechanism of a novel class of phospholipase C, PLCε, and established PLDε as an effector of small GTPases Ras and Pap1. Also, a physiological function of PlCε has been elucidated.1. The CDC25 homology domain of PLCε acts as a guanine nucleotide exchange factor for Rap1, thereby amplifying Rap1-dependent signaling. Stimulation of cells by platelet-derived growth factor (PDGF), induces two phase activation of PLCε through activation of Ras and Rap1. The rapid and initial phase of this activation is mediated by Ras at the plasma membrane, whereas Rap1 is responsible for the prolonged activation at the Golgi apparatus. The CDC25 homology domain is crucial for the prolonged activation of PCLε by Rap1. The Ras/Rap1-dependent activation of PLCε prevents BaF3 cells from undergoing apoptosis and sustains their proliferation.2. Analysis of the spatial and temporal expression patterns of PLCε indicates that in mouse embryos a specific induction of PLCε expression is observed during the course of differentiation of the neural stem cells into the neuronal lineage. In adult, PLCε is expressed abundantly in the heart. The PLCε gene-knockout mice, created by gene targeting, are found to exhibit a phenotype characterized by a market cardiomegaly as well as by overexpression of the heart failure markers as early as 4 weeks of age. Thus, PLCε may play a crucial function in intracellular signaling of the cardiomyocytes by linking the Ras pathway with the Ca^<2+>-calcineurin-NFAT pathway.3. We have isolated a Caenorhabditis elegans mutant worm lacking the PLCε gene. It exhibits a sterile phenotype due to a disorder in transporting the eggs to the uterus, which is presumably caused by defective relaxation of the sphincters of the spermatheca. It is interesting that both the mammals and the nematodes exhibit a similar phenotype carrying a defect in rhythmic muscular contraction.
我们已经阐明了一类新的磷脂酶C,PLCε的调节机制,并建立PLDε作为小GTP酶Ras和Pap 1的效应器。并阐明了PlCε的生理功能. PLCε的CDC 25同源结构域作为Rap 1的鸟嘌呤核苷酸交换因子,从而放大Rap 1依赖的信号传导。血小板衍生生长因子(PDGF)刺激细胞,通过激活Ras和Rap 1诱导PLCε的两相激活。这种激活的快速和初始阶段是由质膜上的Ras介导的,而Rap 1负责高尔基体上的长期激活。CDC 25同源结构域对于Rap 1延长PCLε的激活至关重要。Ras/Rap 1依赖的PLCε激活阻止BaF 3细胞凋亡并维持其增殖. PLCε的时空表达模式的分析表明,在小鼠胚胎中,在神经干细胞向神经元谱系分化的过程中观察到PLCε表达的特异性诱导。在成年人中,PLCε在心脏中大量表达。通过基因靶向产生的PLCε基因敲除小鼠被发现表现出以心脏肥大为特征的表型以及早在4周龄时心力衰竭标志物的过表达。因此,PLCε可能通过连接Ras通路和Ca^2+-calcineurin-NFAT通路,在心肌细胞内信号转导中发挥重要作用.我们分离到一株缺失PLCε基因的秀丽隐杆线虫突变体。它表现出不育表型,这是由于将卵子运送到子宫的障碍,这可能是受精囊括约肌松弛缺陷引起的。有趣的是,哺乳动物和线虫都表现出类似的表型,携带有节奏的肌肉收缩缺陷。

项目成果

期刊论文数量(66)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Juran Kato-Stankiewicz et al.: "Epidermal growth factor stimulation of the ACK1/Dbl pathway in a Cdc42 and Grb2-dependent manner"Biochem.Biophys.Res.Comm.. 284(2). 470-477 (2001)
Juran Kato-Stankiewicz 等人:“表皮生长因子以 Cdc42 和 Grb2 依赖性方式刺激 ACK1/Dbl 途径”Biochem.Biophys.Res.Comm.. 284(2)。
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Kayo Hibino et al.: "Single-and multiple-molecule dynamics of the signaling from H-Ras to c Raf-1 visualized on the plasma membrane of living cells"ChemPhysChem. (印刷中). (2003)
Kayo Hibino 等人:“活细胞膜质上从 H-Ras 到 c Raf-1 的信号传导的单分子和多分子动力学”ChemPhysChem(印刷中)。
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J. Kato-Stankiewicz: "Epidermal growth factor stimulation of the ACK1/Db1 pathway in a Cdc42 and Grb2-dependent manner"Biochem. Biophys. Res. Comm.. 284 (2). 470-477 (2001)
J. Kato-Stankiewicz:“表皮生长因子以 Cdc42 和 Grb2 依赖性方式刺激 ACK1/Db1 通路”Biochem。
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    0
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Y. Liao, et al.: "RA-GEF-1, a guanine nucleotide exchange factor for Rap1, is activated by translocation induced by association with Rap1-GTP and enhances Rap1-dependent B-Raf activation"J. Biol. Chem.. 276 (30). 28478-28483 (2001)
Y. Liao 等人:“RA-GEF-1 是 Rap1 的鸟嘌呤核苷酸交换因子,通过与 Rap1-GTP 结合诱导的易位而被激活,并增强 Rap1 依赖性 B-Raf 激活”J.
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    0
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K. Hibino, et al.: "Single- and multiple-molecule dynamics of the signaling from H-Ras to c Raf-1 visualized on the plasma membrane of living cells"Chemphyschem.. In press. (2003)
K. Hibino 等人:“在活细胞质膜上可视化从 H-Ras 到 c Raf-1 的信号传导的单分子和多分子动力学”Chemphyschem.. 正在出版。
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KATAOKA Tohru其他文献

KATAOKA Tohru的其他文献

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{{ truncateString('KATAOKA Tohru', 18)}}的其他基金

Analysis of the function of Rap1-activating factors which mediate the cross-talks between different species of small G proteins
Rap1激活因子介导不同物种小G蛋白间串扰的功能分析
  • 批准号:
    20390080
  • 财政年份:
    2008
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Mechanism of cell growth regulation by small G proteins
小G蛋白调节细胞生长的机制
  • 批准号:
    17014061
  • 财政年份:
    2005
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Elucidation of the in vivo function of the Ras/Rap effector phospholipase Cε
阐明 Ras/Rap 效应磷脂酶 Cε 的体内功能
  • 批准号:
    17390078
  • 财政年份:
    2005
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of the Regulatory Mechanism and Function of a Novel Class of Phospholipase C, PLCε
一类新型磷脂酶 C PLCε 的调控机制和功能分析
  • 批准号:
    15390093
  • 财政年份:
    2003
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular Mechanism of Regulation of Effector Activities by Small GTP-binding Proteins
小 GTP 结合蛋白调节效应子活性的分子机制
  • 批准号:
    11470034
  • 财政年份:
    1999
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Elucidation of the Molecular Mechanism Underlying the Stimulatory Effect of Posttranslational Lipid Modification of Ras Protein on Activation of Its Effectors
阐明 Ras 蛋白翻译后脂质修饰对其效应子激活的刺激作用的分子机制
  • 批准号:
    09470031
  • 财政年份:
    1997
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The Significance of Posttranslational Modification (Farnesylation) of Ras Protein in Activation of Its Effectors
Ras 蛋白翻译后修饰(法呢基化)对其效应子激活的意义
  • 批准号:
    08457038
  • 财政年份:
    1996
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a Strategy for Selective Inhibition of a Particular Ras Function by Interfering Ras-Effector Interaction
通过干扰 Ras-效应器相互作用来选择性抑制特定 Ras 功能的策略的开发
  • 批准号:
    07557333
  • 财政年份:
    1995
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Mechanism of Intracellular Signaling via Ras Protein
Ras 蛋白的细胞内信号传导机制
  • 批准号:
    06280218
  • 财政年份:
    1994
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
The Function of Yeast Adenylyl Cyclase-Associated Proteins in Regulation of Cell Growth and Cytoskeletal Structure
酵母腺苷酸环化酶相关蛋白在调节细胞生长和细胞骨架结构中的功能
  • 批准号:
    06454167
  • 财政年份:
    1994
  • 资助金额:
    $ 9.34万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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线虫衰老和滞育中的肌醇信号传导
  • 批准号:
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    8852519
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    8394611
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    $ 9.34万
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