title: Activation of serum response element-regulated genes by lysophosphatidic acid.
abstract: 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.
authors.affiliation: Schering-Plough Research Institute, Kenilworth, NJ 07033.
authors.forename: L M
authors.initials: LM
authors.lastname: Perkins
authors.forename: F E
authors.initials: FE
authors.lastname: Ramirez
authors.forename: C C
authors.initials: CC
authors.lastname: Kumar
authors.forename: F J
authors.initials: FJ
authors.lastname: Thomson
authors.forename: M A
authors.initials: MA
authors.lastname: Clark
mesh_terms: D000818:Animals; D001769:Blood; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008246:Lysophospholipids; D012333:RNA, Messenger; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate