A β2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2

A β2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2
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DOI:
10.1126/science.293.5527.98
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发表时间:
2001-07-06
期刊:
影响因子:
56.9
通讯作者:
Hell, JW
Hell, JW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Davare, MA;Avdonin, V;Hell, JW

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大量与异三聚体鸟嘌呤核苷酸结合蛋白(G蛋白)偶联的受体的存在提出了一个问题,即特定的受体如何选择性地调节特定的靶点。我们通过识别一个典型的大分子信号复合体来洞察这个问题。β(2)肾上腺素能受体被发现与其终极效应器之一--C类L型钙通道Ca(V)1.2直接相关。该复合体还含有一个C蛋白、一个腺苷环化酶、环磷酸腺苷依赖的蛋白激酶和平衡磷酸酶PP2A。我们的海马神经元的电生理记录显示了从受体到通道的高度局部化的信号转导。这种信号复合体的组装提供了一种机制,确保通过G蛋白偶联受体进行特异和快速的信号传递。
The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta (2) adrenergic receptor was found to be directly associated with one of its ultimate effecters, the class C L-type calcium channel Ca(v)1.2. This complex also contained a C protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.