Dopamine receptor signaling
Dopamine receptor signaling
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DOI：
10.1081/lrst-200029981
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发表时间：
2004-08-01
影响因子：
2.8
通讯作者：
Trantham-Davidson, H
中科院分区：
文献类型：
--
作者：
Neve, KA;Seamans, JK;Trantham-Davidson, H
多巴胺受体的D-1样（D-1，D-5）和D-2样（D-2，D-3，D-4）类各自具有共同的信号传导特性，这些特性有助于受体类别的定义，尽管已经确定了类别内亚型之间的一些差异。D1样受体信号传导主要由异源三聚体G蛋白Ga（s）和Ga（olf）介导，其引起腺苷酸环化酶、环AMP依赖性蛋白激酶和蛋白磷酸酶-1抑制剂DARPP-32的顺序激活。激活环AMP依赖性蛋白激酶和抑制蛋白磷酸酶1的联合作用导致的磷酸化增加调节许多受体、酶、离子通道和转录因子的活性。D-1或一种新的D-1样受体也通过磷脂酶C依赖性和环AMP非依赖性的细胞内钙的动员发出信号。D-2样受体信号传导由异源三聚体G蛋白Ga（i）和Ga（o）介导。这些百日咳毒素敏感性G蛋白通过其G α亚基调节一些效应物，如腺苷酸环化酶，但由于受体诱导的G β亚基释放，调节更多的效应物，如离子通道、磷脂酶、蛋白激酶和受体酪氨酸激酶。除了多巴胺受体和G蛋白之间的相互作用，其他蛋白质：蛋白质相互作用，如受体寡聚化或受体与支架和信号转换蛋白的相互作用是调节多巴胺受体信号传导的关键。
The D-1-like (D-1, D-5) and D-2-like (D-2, D-3, D-4) classes of dopamine receptors each has shared signaling properties that contribute to the definition of the receptor class, although some differences among subtypes within a class have been identified. D1-like receptor signaling is mediated chiefly by the heterotrimeric G proteins Galpha(s) and Galpha(olf), which cause sequential activation of adenylate cyclase, cylic AMP-dependent protein kinase, and the protein phosphatase-1 inhibitor DARPP-32. The increased phosphorylation that results from the combined effects of activating cyclic AMP-dependent protein kinase and inhibiting protein phosphatase 1 regulates the activity of many receptors, enzymes, ion channels, and transcription factors. D-1 or a novel D-1-like receptor also signals via phospholipase C-dependent and cyclic AMP-independent mobilization of intracellular calcium. D-2-like receptor signaling is mediated by the heterotrimeric G proteins Galpha(i) and Galpha(o). These pertussis toxin-sensitive G proteins regulate some effectors, such as adenylate cyclase, via their Galpha subunits, but regulate many more effectors such as ion channels, phospholipases, protein kinases, and receptor tyrosine kinases as a result of the receptor-induced liberation of Gbetagamma subunits. In addition to interactions between dopamine receptors and G proteins, other protein:protein interactions such as receptor oligomerization or receptor interactions with scaffolding and signal-switching proteins are critical for regulation of dopamine receptor signaling.