PMID- 15913563 OWN - NLM STAT- MEDLINE DCOM- 20050809 LR - 20151119 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 332 IP - 3 DP - 2005 Jul 8 TI - Dexras1 blocks receptor-mediated heterologous sensitization of adenylyl cyclase 1. PG - 913-20 AB - Dexras1/AGS1/RasD1 is a member of the Ras superfamily of monomeric G proteins and has been suggested to disrupt receptor-G protein signaling. We examined the ability of Dexras1 to modulate dopamine D(2L) receptor regulation of adenylyl cyclase (AC) type 1 in HEK293 cells. Acute D(2L) receptor-mediated inhibition of A23187-stimulated AC1 activity (IC50, 4.0+/-1.4 nM; 50+/-3% inhibition) was not altered in the presence of Dexras1 (IC50, 2.4+/-1.3 nM, 50+/-1% inhibition); however, Dexras1 blocked acute D(2L) receptor-mediated activation of ERK 1/2 by approximately 50%. Heterologous sensitization of AC1 induced by persistent activation of D(2L) receptors was completely blocked by Dexras1 under basal and A23187-stimulated conditions. The block of sensitization was concentration-dependent and was not observed with a nucleotide binding-deficient Dexras1G31V mutant. Sensitization of AC1 was Gbetagamma-dependent as demonstrated using the C-terminus of beta-adrenergic receptor kinase (betaARK-ct). These data suggest that Dexras1 selectively regulates receptor-mediated Gbetagamma signaling pathways. FAU - Nguyen, Chau H AU - Nguyen CH AD - Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47909, USA. FAU - Watts, Val J AU - Watts VJ LA - eng GR - DA13680/DA/NIDA NIH HHS/United States GR - MH60397/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (G-protein Beta gamma) RN - 0 (GTP-Binding Protein beta Subunits) RN - 0 (GTP-Binding Protein gamma Subunits) RN - 0 (RASD1 protein, human) RN - 0 (Receptors, Dopamine D2) RN - 0 (Recombinant Proteins) RN - 0 (dopamine D2L receptor) RN - 20OP60125T (Quinpirole) RN - 37H9VM9WZL (Calcimycin) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go) RN - EC 3.6.5.2 (ras Proteins) RN - EC 4.6.1.1 (Adenylyl Cyclases) SB - IM MH - Adenylyl Cyclases/genetics/*metabolism MH - Binding Sites/genetics MH - Calcimycin/pharmacology MH - Cell Line MH - Cyclic AMP/metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - GTP-Binding Protein alpha Subunits, Gi-Go/metabolism MH - GTP-Binding Protein beta Subunits/metabolism MH - GTP-Binding Protein gamma Subunits/metabolism MH - GTP-Binding Proteins/genetics/metabolism/*pharmacology MH - Humans MH - Kinetics MH - Mutagenesis, Site-Directed MH - Quinpirole/pharmacology MH - Receptors, Dopamine D2/genetics/metabolism MH - Recombinant Proteins/genetics/metabolism/pharmacology MH - Signal Transduction MH - Transfection MH - ras Proteins/genetics/metabolism/*pharmacology EDAT- 2005/05/26 09:00 MHDA- 2005/08/10 09:00 CRDT- 2005/05/26 09:00 PHST- 2005/05/10 00:00 [received] PHST- 2005/05/11 00:00 [accepted] PHST- 2005/05/26 09:00 [pubmed] PHST- 2005/08/10 09:00 [medline] PHST- 2005/05/26 09:00 [entrez] AID - S0006-291X(05)01021-1 [pii] AID - 10.1016/j.bbrc.2005.05.041 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2005 Jul 8;332(3):913-20. doi: 10.1016/j.bbrc.2005.05.041.