Sphingosine-1-phosphate (S1P) caused dose-dependent and time-dependent increases in c-fos mRNA. Pretreatment with pertussis toxin (PTX; 100 ng/ml×24 h) reduced c-fos activation by S1P (100 μM-187±6% vs. 411±27%) and lysophosphatidic acid (LPA; 100 μM-90±34% vs. 188±41%), but not by sphingosylphosphorylcholine (SPC; 100 μM-390±47% vs. 420±44%). RT-PCR analysis and sequencing demonstrated the presence of previously unidentified LPA-responsive Endothelial Differentiation Gene (EDG) receptor mRNAs in C6 cells: EDG-2 and EDG-4.
Bibliographical noteFunding Information:
This research was supported by the National Institutes of Health (DK41204 and accompanying Minority Supplemental Grant, and Systems and Integrative Biology training grant GM08322-11) and by a pre-doctoral fellowship from the Horace Rackham School of Graduate Studies, University of Michigan.
- Early response gene
- Lysophosphatidic acid