REGULATORY MECHANISM OF PHOSPHOLIPASE D IN CELL GROWTH AND SURVIVAL SIGNALING

磷脂酶 D 在细胞生长和生存信号传导中的调节机制

• 批准号: 14580646
• 负责人: BANNO Yoshiko
• 金额: $ 2.3万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580646/
• 关键词: PHOSPHOLIPASE D; PHOSPHATIDYLINOSITOL 3-KINASE; SURVIVAL SIGNALING; AKT; ERK; SPHINGOSINE 1-PHOSPHATE; 膜脂質変換酵素; 細胞増殖

Phospholipase D has been known to be important signaling enzyme to regulate cell proliferation and survival. Two types of PLD(1,2) have been cloned in mammalian tissues and cells. The PLD1 and PLD2 are differently regulated and distributed in the cells. Sphingosine 1-phosphate(S1P) stimulation of S1P_3-overexpressing CHO cells induced activation of PLD, PI3-kinase, and Akt. S1P-induced activation of PI3-kinase and Akt was abrogated by 1-butanol, which inhibited phosphatidic acid(PA) formation by PLD. Overexpression of the wild-type PLD1,2 resulted in increased activation of Akt, ERK and p70S6 kinase in response to S1P. Actinomycine D(AchD) induced apoptosis in CHO cells, and the apoptosis was prevented by overexpression of PLD1,2. The treatment of CHO cells with AchD induced activation of survival signaling(PI3K, Akt, ERK, p70S6K) at earlier times of apoptosis. The activities of survival signaling were increased by overexpression of PLD1,2. These results demonstrate that PLD participates in the potentiation of survival signaling activation. We have found that PLD1 play a role in melanogenesis of mouse B16 melanoma cells. It has been shown that PLD1 negatively regulated the melanogenic signaling by modulating the expression of tyrosinase in B16 melanoma cells.

已知磷脂酶 D 是调节细胞增殖和存活的重要信号酶。两种类型的 PLD(1,2) 已在哺乳动物组织和细胞中克隆。 PLD1和PLD2在细胞中受到不同的调节和分布。 1-磷酸鞘氨醇 (S1P) 刺激 S1P_3 过表达的 CHO 细胞可诱导 PLD、PI3 激酶和 Akt 的激活。 1-丁醇可消除 S1P 诱导的 PI3 激酶和 Akt 激活，从而抑制 PLD 形成磷脂酸 (PA)。野生型 PLD1,2 的过度表达导致 Akt、ERK 和 p70S6 激酶响应 S1P 的激活增加。 Actinomycine D(AchD) 诱导 CHO 细胞凋亡，过表达 PLD1,2 可以阻止细胞凋亡。用 AchD 处理 CHO 细胞可在细胞凋亡早期诱导生存信号（PI3K、Akt、ERK、p70S6K）的激活。 PLD1,2 的过度表达增加了生存信号的活性。这些结果表明 PLD 参与生存信号激活的增强。我们发现 PLD1 在小鼠 B16 黑色素瘤细胞的黑色素生成中发挥作用。研究表明，PLD1 通过调节 B16 黑色素瘤细胞中酪氨酸酶的表达来负向调节黑色素生成信号。

项目成果

Terada, N.: "Compartmenttation of the mouse cerebellar cortex by sphingosine kinase."J.Comp.Neurol.. 469. 119-127 (2004)

Terada, N.：“鞘氨醇激酶对小鼠小脑皮质的区室化。”J.Comp.Neurol.. 469. 119-127 (2004)

Ohguchi, K. et al.: "Involvement of Phospholipase D1 in Melanogenesis of Mouse B16 Melanoma Cells."J.Biol.Chem.. 279. 3408-3412 (2004)

Ohguchi, K. 等人：“磷脂酶 D1 参与小鼠 B16 黑色素瘤细胞的黑色素生成。”J.Biol.Chem. 279. 3408-3412 (2004)

Tin, Y.et al.: "Inhibitory effect of local anesthetics on bradykinin-induced phospholipase D in rat pheochromocytoma PC12 cells."Chin.Anes.Analg.. 95. 88-97 (2002)

Tin, Y. 等：“局部麻醉剂对大鼠嗜铬细胞瘤 PC12 细胞中缓激肽诱导的磷脂酶 D 的抑制作用。”Chin.Anes.Analg.. 95. 88-97 (2002)

Yamada Y.: "Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer."J.Mol.Med.. 81. 126-131 (2003)

Yamada Y.：“磷脂酶 D2 基因多态性与结直肠癌患病率的关联。”J.Mol.Med.. 81. 126-131 (2003)

Ohguchi, K.: "Involvement of Phospholipase D1 in Melanogenesis of Mouse B16 Melanoma Cells."J.Biol.Chem.. 279. 3408-3412 (2004)

Ohguchi, K.：“磷脂酶 D1 参与小鼠 B16 黑色素瘤细胞的黑色素生成。”J.Biol.Chem.. 279. 3408-3412 (2004)