Activation of serum response element by D2 dopamine receptor is governed by Gbetagamma-mediated MAPK and Rho pathways and regulated by RGS proteins

• Published in: Pharmacology Vol. 79; no. 2; pp. 114 - 121
• Main Authors: Ho, Guyu, Wang, Yuren, Jones, Philip G, Young, Kathleen H
• Format: Journal Article
• Language: English
• Published: Switzerland 2007
• Subjects: Animals; beta-Adrenergic Receptor Kinases - metabolism; CHO Cells; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Genes, Reporter; GTP-Binding Protein alpha Subunits - physiology; GTP-Binding Protein beta Subunits - physiology; GTP-Binding Protein gamma Subunits - physiology; Heterotrimeric GTP-Binding Proteins - physiology; Mitogen-Activated Protein Kinases - physiology; Pertussis Toxin - pharmacology; Quinpirole - pharmacology; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - physiology; RGS Proteins - physiology; rho GTP-Binding Proteins - physiology; Serum Response Element; Signal Transduction
• ISSN: 0031-7012

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 beta-adrenergic receptor kinase C-terminus, implicating the involvement of Galpha(i )and Gbetagamma in the signal transduction. Furthermore, using MEK inhibitors and dominant negative mutants of RhoA, Rac1, and Cdc42, we showed that the Gbetagamma-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.