Activation of serum response element-regulated genes by lysophosphatidic acid

Lysophosphatidic acid (LPA) is an important constituent of serum and shares its mitogenic activity. Serum induction of several genes is regulated, at least in part, by sequences related to the c-Fos serum response element (SRE). A Rat-2 fibroblast cell line containing the beta-galactosidase reporter gene under SRE control was treated with LPA. Lysophosphatidic acid induced a time- and dose-dependent increase in beta-galactosidase activity. After 5 hours of treatment with 1-oleoyl-LPA a 3-fold increase in beta-galactosidase activity was observed. In contrast, endogenous Alkaline Phosphatase activity did not change in parallel with the beta-galactosidase activity indicating that the induction was specific. Various LPAs with different acyl groups in the sn-1 position induced beta-galactosidase activity with a rank order potency of 1-oleoyl-LPA > 1-palmitoyl-LPA > or = 1-myristoyl-LPA > 1-stearoyl-LPA. Phosphatidic acid was approximately equal to 1-stearoyl-LPA. Neither the calcium ionophore (A23187) nor 12-O-tetradecanoylphorbol 13-acetate, induced beta-galactosidase activity. These data suggest that LPA may exert some of its effects by regulation of SRE controlled genes.