Rhes and AGS1/Dexras1 Affect Signaling by Dopamine D1 Receptors Through Adenylyl Cyclase
Rhes and AGS1/Dexras1 Affect Signaling by Dopamine D1 Receptors Through Adenylyl Cyclase
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DOI：
10.1002/jnr.22604
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发表时间：
2011-06-01
影响因子：
4.2
通讯作者：
He, YouE
中科院分区：
文献类型：
--
作者：
Harrison, Laura M.;He, YouE
The GTP binding proteins Rhes and AGS1/Dexras1 define a subfamily of the Ras superfamily and have been shown to affect signaling by G-protein-coupled receptors. We tested the effects of both proteins at an early stage of signaling by dopamine receptors, activation of adenylyl cyclase. Rhes decreased dopamine D1 receptor agonist-stimulated cAMP accumulation in a pertussis toxin-sensitive manner. It had no effect on cAMP accumulation in the absence of agonist. AGS1/Dexras1, on the other hand, decreased cAMP accumulation in both vehicle-treated and agonist-treated cells, resulting in a higher percentage of stimulation by agonist or a higher signal-to-noise ratio. The effects of AGS1/Dexras1 on cAMP accumulation were not blocked by pertussis toxin, suggesting that it may produce these effects through interaction with a G(alpha)i monomer. Both Rhes and AGS1/Dexras1 were associated with GTP-bound G(alpha)i in pull-down assays. However, Rhes had no effect on the ability of activated D2 receptor to inhibit cAMP. Neither Rhes nor AGS1/Dexras1 interacted with the D1 receptor in pull-down assays. These findings show that, in addition to its well-known effects on signaling through Gi-coupled receptors, AGS1/Dexras1 can affect signaling through a Gs/olf-coupled receptor. Furthermore, the results suggest that Rhes exerts some of its effects by interacting with G(alpha)i. (C) 2011 Wiley-Liss, Inc.
