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Molecular mechanism of inhibition of cell motility

抑制细胞运动的分子机制

基本信息

批准号：
16590163
负责人：
SUGIMOTO Naotoshi
金额：
$ 2.3万
依托单位：
Kanazawa University Graduate School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590163/
关键词：
sphingosine-1-phosphate cell migration signal transduction small G protein

项目摘要

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many of these responses are mediated by S1P receptors, S1P_1/EDG1, S1P_3/EDG3, and S1P_2/EDG5. We previously showed that S1P_2/EDG5, via G_<12> and G_<13> proteins, mediated inhibiton of insulin-like growth factor-I (IGF-I)-induced Rac activation and cell migration, whereas S1P_1/EDG1 and S1P_3/EDG3 each alone, via G_1 protein, mediated Rac activation and stimulation of cell migration. However, it is not known how G_<12> and G_<13> proteins mediate inhibition of Rac and cell migration in S1P_2/EDG5 signaling. We found that the pretreatment with C3 toxin, which inactivates Rho, and the expresson of dominat negative Rho A prevented S1P_2/EDG5-mediated inhibition of Rac and cell migration. On other hand, the expression of constitutively active Rho inhibited IGF-I induced Rac activation and cell migration. However, Rho kinase inhibitors did not affect S1P_2/EDG5-mediated inhibition of Rac or cell migration. These results indicate that Rho, but not Rho kinase, mediates inhibition of Rac activity and cell mobility on stimulation of S1P_2/EDG5.

鞘氨醇-1-磷酸（S1 P）是一种具有生物活性的溶血磷脂，可在多种细胞类型中诱导多种生物学反应。这些反应中的许多由S1 P受体S1P_1/EDG 1、S1P_3/EDG 3和S1P_2/EDG 5介导。我们以前的研究表明，S1P_2/EDG_5通过G_1<12>和G_2<13>蛋白介导胰岛素样生长因子-I（IGF-I）诱导的Rac活化和细胞迁移，而S1P_1/EDG_1和S1P_3/EDG_3单独通过G_1蛋白介导Rac活化和细胞迁移。然而，G_1<12>和G_2<13>蛋白如何在S1P_2/EDG 5信号转导中介导Rac抑制和细胞迁移尚不清楚。我们发现，用C3毒素预处理，使Rho失活，并表达显性负性RhoA，可阻止S1P_2/EDG 5介导的Rac抑制和细胞迁移。另一方面，组成型活性Rho的表达抑制IGF-I诱导的Rac活化和细胞迁移。然而，Rho激酶抑制剂不影响S1P_2/EDG 5介导的Rac抑制或细胞迁移。这些结果表明，Rho，而不是Rho激酶，介导抑制Rac活性和细胞运动性对刺激S1P_2/EDG 5。

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion

DOI：
10.1161/01.atv.0000178171.61754.cd
发表时间：
2005-09-01
期刊：
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
影响因子：
8.7
作者：
Sakamoto, T;Ishibashi, T;Maruyama, Y
通讯作者：
Maruyama, Y

Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle.

II 类磷酸肌醇 3-激酶 α-异构体调节 Rho、肌球蛋白磷酸酶和血管平滑肌的收缩。

DOI：
发表时间：
2006
期刊：
Biochem J. 394(Pt 3)
影响因子：
0
作者：
Wang Y;Yoshioka K;Azam MA;Kimura T;Kuwaki T;Takuwa Y.
通讯作者：
Takuwa Y.

Rho-dependent, Rho kinase-independent inhibitory regulation of Rac and cell migration by LPA1 receptor in Gi-inactivated CHO cells

DOI：
10.1016/j.yexcr.2006.02.020
发表时间：
2006-06-10
期刊：
EXPERIMENTAL CELL RESEARCH
影响因子：
3.7
作者：
Sugimoto, Naotoshi;Takuwa, Noriko;Takuwa, Yoh
通讯作者：
Takuwa, Yoh

Calcium-dependent regulation of Rho and myosin phosphatase in vascular smooth muscle

血管平滑肌中 Rho 和肌球蛋白磷酸酶的钙依赖性调节

DOI：
发表时间：
2005
期刊：
Biomedical Review 16
影响因子：
0
作者：
Yoh Takuwa;Kazuaki Yoshioka;Noriko Takuwa;Yu Wang;Mohammed Ali Azam;Naotoshi Sugimofo
通讯作者：
Naotoshi Sugimofo

Involvement of the betagamma subunits of G proteins in the cAMP response induced by stimulation of the histamine H1 receptor.

G 蛋白的 betaamma 亚基参与刺激组胺 H1 受体诱导的 cAMP 反应。