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Nucleic Acids Research, 1994, Vol. 22, No. 3 450-452
© 1994


MOLECULAR BIOLOGY

Activation of serum response element-regulated genes by lysophosphatidic acid

Louise M. Perkins, Fernando E. Ramirez, Fernando E. Kumar, Chandra C. Kumar, Fiona J. Thomson and Mike A. Clark

Schering-Plough Research Institute 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA

Received September 7, 1993. Accepted December 16, 1993.

Lysophosphatldic acid (LPA) is an important constituent of serum and shares its mitogenlc 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 flbroblast cell line containing the ß-galactosidase reporter gene under SRE control was treated with LPA. Lysophosphatldic acid induced a time- and dose-dependent increase in ß-galactosldase activity. After 5 hours of treatment with 1-oleoyl-LPA a 3-fold increase in ß-galactosidase activity was observed. In contrast, endogenous alkaline phosphatase activity did not change in parallel with the /3-galactosidase activity indicating that the induction was specific. Various LPAs with different acyl groups in the sn-1 position induced ß-galactosidase activity with a rank order potency of 1-oleoyl-LPA > 1-palmitoyl-LPA ≥ 1-myrlstoyl-LPA > 1-stearoyl-LPA. Phosphatldic acid was approximately equal to 1-stearoyl-LPA. Neither the calcium ionophore (A23187) nor 12-O-tetradecanoylphorbol 13-acetate, Induced ß-galactosidase activity. These data suggest that LPA may exert some of its effects by regulation of SRE controlled genes.


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