课题基金 / 基金详情

The molecular mechanism of p160ROCK-mediated signaling pathway

The molecular mechanism of p160ROCK-mediated signaling pathway
p160ROCK介导的信号通路的分子机制
批准号:
10670120
负责人:
ISHIZAKI Toshimasa
金额:
$1.79万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1998
资助国家:
日本
项目状态:
已结题
起止时间:
1998 至 1999

项目摘要

项目成果

ISHIZAKI Toshimasa的其他基金

相似基金

相关文献

中文摘要
翻译
我们发现Rho相关卷曲螺旋形成蛋白激酶(p160 ROCK)是一种丝氨酸/苏氨酸激酶。p160 ROCK是小G T β Rho的效应蛋白的成员,并特异性结合Rho的活化形式,从而在这种结合时被活化。在成纤维细胞和上皮细胞的粘附实验中,该激酶参与肌动蛋白应力纤维的形成和由Rho介导的粘着斑。此外,在nuroblastama N1 E-115细胞中,该激酶通过调节细胞皮层的收缩力而诱导细胞变圆。因此,认为p160 ROCK定位于细胞中的几个特定位点并磷酸化几种底物。最近,我们开发了ROCK的特异性抑制剂,我们将其命名为Y-27632。该化合物在激酶结构域与ATP竞争。利用该化合物,我们报道了Rho/ROCK通路对高血压模型大鼠血压的调节作用,表明该通路参与了高血压的病理生理过程。然而,Rho/ROCK信号通路的分子机制尚不清楚,本研究通过分离p160 ROCK的磷酸化底物,试图了解p160 ROCK介导的信号通路的分子机制。结论:1. p160 ROCK通过磷酸化和激活LIM-激酶来调节Confilin/ADF的磷酸化。p160 ROCK与Rho的另一个效应分子mDia在Rho介导的肌动蛋白应力纤维形成和粘着斑形成中协同作用。
英文摘要
We found Rho-associated coiled coil forming protein kinase (p160ROCK) is serine/threonine kinase. p160ROCK is a member of effector protein of small GTPase Rho and specisically binds to activated form of Rho thereby becomes activated upon this binding. During transfction experiments in fibroblast and eptherial cells, this kinase is involved in formation of actin stress fibers and focal adhesions mediated by Rho. In addition to this, in nuroblastama N1E-115 cell this kinase induces cell rounding by regulating contractile force at cell cortex.Thus, it is thought that p160ROCK is localized to several specific sites in the cell and phosphorylates several substrates.Recently, we developed a specific inhibitor of ROCK, we named it Y-27632. This compound competes with ATP at the kinase domain. Using this compound, we reported that Rho/ROCK pathway regulates blood pressure in hypertension model rats, indicating that this pathway is involved in the pathophysiology of hypertension. However, the molecular mechanism of Rho/ROCK pathway is not clearly known.In this study, we try to understand the molecular mechanism (s) of p160ROCK-mediated signaling pathway (s) through the isolation of phosphorylated substrates for p160ROCK.As a result, our major findings are as follows,1. p160ROCK regulates Confilin/ADF phosphorylaytion through phosphorylation and activation of LIM-kinase.2. p160ROCK cooperates with mDia, another effector molecule of Rho, on Rho-mediated actin stress fiber formation and focal adhesion formation.
期刊论文(6)
专著(0)
科研奖励(0)
会议论文
Ishizaki T. et al: "Pharmacological properties of Y-27632, a specific inhibitor of Rho-associated kinases"Molecular Pharmacology. (in press).
Ishizaki T. 等人:“Y-27632 的药理学特性,Rho 相关激酶的特异性抑制剂”分子药理学。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Maekawa,M., et al.: "Siganling from Rho to actin cytoskeleton through protein kinase ROCK and LIM-kinase"Science. 285. 895-898 (1999)
Maekawa,M., et al.:“通过蛋白激酶 ROCK 和 LIM 激酶从 Rho 到肌动蛋白细胞骨架的 Siganling”《科学》。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Watanabe,N.et al.: "Cooperation between mDial and ROCK in Rho-induced actin reorganization"Nature Cell Biology. 1. 136-143 (1999)
Watanabe,N.等人:“mDial 和 ROCK 在 Rho 诱导的肌动蛋白重组中的合作”《自然细胞生物学》。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Sahai,E.et al.: "Transformation mediated by RhoA requires activity of ROCK kinases"Current Biology. 9. 136-145 (1999)
Sahai,E.等人:“RhoA 介导的转化需要 ROCK 激酶的活性”《当代生物学》。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
The role of mDia, a Rho effector molecule, in tumorigenesis
  • 批准号:
    22501011
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 资助金额:
    $2.83万
  • 财政年份:
    2011
  • 负责人:
    ISHIZAKI Toshimasa
  • 依托单位:
Functional interaction between Rho effector proteins
  • 批准号:
    18590262
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 资助金额:
    $2.5万
  • 财政年份:
    2006
  • 负责人:
    ISHIZAKI Toshimasa
  • 依托单位:
Signal Crosstalk between Rho and Tyrosine phosphorylation
  • 批准号:
    12670112
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 资助金额:
    $2.18万
  • 财政年份:
    2000
  • 负责人:
    ISHIZAKI Toshimasa
  • 依托单位:
国内基金
海外基金
NLK-ROCK1信号轴调控巨噬细胞胞葬作用在脓毒症肺损伤中的机制研究
  • 批准号:
    JCZRQNB202600383
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2026
  • 负责人:
  • 依托单位:
西黄丸介导RhOA-ROCK轴重构基质剪切力改善前列腺癌骨转移前龛“瘀毒”微环境的机制研究
  • 批准号:
    2026JJ81061
  • 项目类别:
    省市级项目
  • 资助金额:
    --
  • 批准年份:
    2026
  • 负责人:
    吴泳蓉
  • 依托单位:
基于RhoA/ROCK2信号通路探讨六味地黄丸调控氧化应激与突触可塑性改善自闭症谱系障碍的机制研究