Intracellular and extracellular metabolism of lipid mediators- DGK and LPA

我们研究了在不同细胞中表达的两种脂质代谢酶，二酰基甘油激酶（DGK）和脂质磷酸磷酸酶（LPP）的功能。DGK γ被发现作为Rac-1的抑制因子，从而抑制成纤维细胞中板层基的形成。这种DGK同工酶也被转移到各种细胞的细胞核中，导致细胞生长受到抑制。DGK δ的PH结构域被认为参与了该同工酶的质膜易位。克隆了DGK同工酶的第10个成员DGK kappa，并对其酶学性质进行了表征。对于作用于细胞外表面的LPP，我们发现LPP-1或LPP-3的表达对多种卵巢癌细胞系的生长有明显的抑制作用，提示细胞外溶磷脂酸代谢在癌细胞增殖中的重要性。

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.