Activation of serum response element by D2 dopamine receptor is governed by Gbetagamma-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 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.
Ho
Guyu
G
Wyeth Neuroscience Research, Wyeth Research, Princeton, N.J., USA.
Wang
Yuren
Y
Jones
Philip G
PG
Young
Kathleen H
KH
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*
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