Activation of Serum Response Element by D2 Dopamine Receptor Is Governed by Gβγ-Mediated MAPK and Rho Pathways and Regulated by RGS Proteins

In this study, we investigated the activation of the serum response element (SRE) by the D2 dopamine receptor (D2R) agonist quinpirole. Stimulation of CHO cells expressing the D2R by quinpirol evoked a dose-dependent SRE activation, which was completely blocked by overnight treatment of pertussis toxin or by co-expression of the β-adrenergic receptor kinase C-terminus, implicating the involvement of Gαi and Gβγ in the signal transduction. Furthermore, using MEK inhibitors and dominant negative mutants of RhoA, Rac1, and Cdc42, we showed that the Gβγ-mediated activation of the SRE in CHO cells utilizes both MAPK and Rho pathways. Expression of either regulator of G protein signaling 2 or 4 (RGS2 or RGS4) proteins significantly attenuated the quinpirole-induced SRE activation. These results delineate the signaling pathways which couple D2 receptor to the transcriptional activation of SRE and demonstrate a modulatory role for RGS proteins in these processes.