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. 2012 Oct 12;7(10):e47312. doi: 10.1371/journal.pone.0047312

Figure 6. Riluzole upregulates the expression of genes associated with the TGFβ signaling pathway.

Figure 6

A. Model of riluzole effect on Smad linker phosphorylation. Riluzole inhibits the phosphorylation of AKT at S473 and T308. As a result of AKT inactivation, GSK3 phosphorylation at the AKT site is decreased, resulting in GSK3 activation. GSK3 phosphorylates Smad2 at the cluster of serines 245/250/255 and Smad3 at serine 204. The consequences of these phosphorylation events on Smad2 and Smad3 activities will likely depend on the promoters of the TGFβ target genes. B and C. Riluzole treatment increases the expression of the INHBB and PLAU genes respectively in the three independent melanoma cell lines A2058, UACC903 and C8161. mRNA from these three melanoma cell lines untreated or treated with riluzole for 24 hours were analyzed by real-time PCR for the expression of the INHBB and PLAU genes. White bars: untreated cells. Dark bars: Riluzole-treated cells. *, P<0.05, compared with untreated cells (t test).