Intracellular and extracellular metabolism of lipid mediators- DGK and LPA

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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.