AGS3 表达对 D(2L)多巴胺受体介导的腺苷酸环化酶信号的影响差异。
Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling.
机构信息
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
出版信息
Cell Mol Neurobiol. 2013 May;33(4):551-8. doi: 10.1007/s10571-013-9925-8. Epub 2013 Mar 17.
Abstract
Activator of G protein signaling 3 (AGS3) binds Gα(i) subunits in the GDP-bound state, implicating AGS3 as an important regulator of Gα(i)-linked receptor (e.g., D2 dopamine and μ-opioid) signaling. We examined the ability of AGS3 to modulate recombinant adenylyl cyclase (AC) type 1 and 2 signaling in HEK293 cells following both acute and persistent activation of the D(2L) dopamine receptor (D(2L)DR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D(2L)DR modulation of AC1 or AC2 activity. AGS3 also promoted desensitization of D(2L)DR-mediated inhibition of AC1, whereas desensitization of D(2L)DR-mediated AC2 activation was significantly attenuated. Additionally, AGS3 reduced D(2L)DR-mediated sensitization of AC1 and AC2. These data suggest that AGS3 is involved in altering G protein signaling in a complex fashion that is effector-specific and dependent on the duration of receptor activation.
摘要
G 蛋白信号转导激活因子 3（AGS3）与 GDP 结合状态下的 Gα(i)亚基结合，表明 AGS3 是 Gα(i)偶联受体（如 D2 多巴胺和 μ 阿片受体）信号转导的重要调节剂。我们在急性和持续激活 D2L 多巴胺受体（D2LDR）后，研究了 AGS3 对重组腺苷酸环化酶（AC）1 型和 2 型信号的调节能力。AGS3 表达可适度增强急性喹吡罗诱导的 D2LDR 对 AC1 或 AC2 活性的调节作用。AGS3 还促进了 D2LDR 介导的 AC1 失活脱敏，而 D2LDR 介导的 AC2 激活的失活脱敏则明显减弱。此外，AGS3 降低了 D2LDR 介导的 AC1 和 AC2 的敏化作用。这些数据表明，AGS3 以一种效应物特异性和受体激活持续时间依赖性的复杂方式参与改变 G 蛋白信号转导。
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