Intracellular and extracellular metabolism of lipid mediators- DGK and LPA

脂质介质 DGK 和 LPA 的细胞内和细胞外代谢

• 批准号: 16590234
• 负责人: KANOH Hideo
• 金额: $ 2.24万
• 依托单位: Sapporo Medical University
• 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-16590234/
• 关键词: Diacylglycerol; Diacylglycerol kinase; Lipid phosphate phosphatase; Phosphatidic acid; Phosphatidic acid phosphatase; Signal transduction; ジアシルグリセロール キナーゼ; 脂質性メデイエーター; 細胞情報伝達; リゾホスファチジン酸

We investigated the function of two lipid-metabolizing enzymes, diacylglycerol kinase (DGK) and lipid phosphate phosphatase (LPP), expressed in various cells. DGK gamma was found to act as a suppressor of Rac-1, thus inhibiting lamellipodium formation in fibroblasts. This DGK isozyme was also translocated into the nuclei of various cells, resulting in an inhibition of cell growth. The PH domain of DGK delta was suggested to be involved in the plasma membrane translocation of this isozyme. The tenth member of DGK isozyme, DGK kappa, was cloned and its enzymatic properties were characterized. In the case of LPP, which acts at the outer cell surface, we found that the expression of LPP-1 or LPP-3 caused a marked suppression of the growth of various ovarian cancer cell lines, suggesting the importance of metabolizing extracellular lyso-phosphatidic acid in cancer cell proliferation.

我们研究了两种脂质代谢酶，二酰基甘油激酶（DGK）和脂质磷酸磷酸酶（LPP），在各种细胞中表达的功能。发现DGK γ作为Rac-1的抑制剂，从而抑制成纤维细胞中的板状伪足形成。这种DGK同工酶也被易位到各种细胞的细胞核中，导致细胞生长的抑制。DGK δ的PH结构域可能参与该同工酶的质膜转位。克隆了DGK同工酶的第10个成员DGKkappa，并对其酶学性质进行了研究。在作用于细胞外表面的LPP的情况下，我们发现LPP-1或LPP-3的表达引起各种卵巢癌细胞系的生长的显著抑制，这表明代谢细胞外溶血磷脂酸在癌细胞增殖中的重要性。

项目成果

Gene expression, cellular localization and enzymatic activity of diacylglycerol kinase isozymes in rat ovary and placenta.

大鼠卵巢和胎盘中二酰甘油激酶同工酶的基因表达、细胞定位和酶活性。

• 期刊: Cell Tissue Res. in press
• 作者: Toya;M. et al.
• 通讯作者: M. et al.

Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lamellipodium formation.

二酰基甘油激酶 γ 作为 Rac1 和板状足形成的上游抑制因子。

• 发表时间: 2004
• 期刊: J.Biol.Chem. 279(27)
• 作者: Okamoto R;Irie K;Yamada A;Katata T;Fukuhara A;Takai Y.;Tsushima S. et al.
• 通讯作者: Tsushima S. et al.

Identification and characterization of a novel human type II diacylglycerol kinase, DGKκ

• DOI: 10.1074/jbc.m500669200
• 发表时间: 2005-12-02
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Imai, S;Kai, M;Sakane, F
• 通讯作者: Sakane, F

Identification and characterization of a novel human type II chiaphislyrolkinase, DGKκ.

新型人 II 型 Chiaphislyrolkinase DGKκ 的鉴定和表征。

• 发表时间: 2005
• 期刊: J. Biol. Chem. 280(48)
• 作者: Imai;S. et al.
• 通讯作者: S. et al.

広川生物薬科学講座 Vol.4(石橋、市川、堅田編)

广川生物制药科学课程第4卷（石桥、市川、片田主编）

• 发表时间: 2005
• 作者: 坂根郁夫;山田恵子;加納英雄
• 通讯作者: 加納英雄