title: Activation of serum response element by D2 dopamine receptor is governed by Gbetagamma-mediated MAPK and Rho pathways and regulated by RGS proteins.
abstract: 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.
authors.affiliation: Wyeth Neuroscience Research, Wyeth Research, Princeton, N.J., USA.
authors.forename: Guyu
authors.initials: G
authors.lastname: Ho
authors.forename: Yuren
authors.initials: Y
authors.lastname: Wang
authors.forename: Philip G
authors.initials: PG
authors.lastname: Jones
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Young
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D044385:GTP-Binding Protein alpha Subunits / Q000502:physiology; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology; D017930:Genes, Reporter; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D020710:RGS Proteins / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D027602:Serum Response Element; D015398:Signal Transduction; D051552:beta-Adrenergic Receptor Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020710:RGS Proteins; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D037342:Pertussis Toxin; D051552:beta-Adrenergic Receptor Kinases; D020928:Mitogen-Activated Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins