beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation.
beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation.
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Beta-arrestin1与G蛋白亚基β1GAMMA2相互作用，并促进beta1gamma2依赖性AKT信号，以用于NF-kappab激活。
DOI：
10.1042/bj20081561
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Ye RD
中科院分区：
文献类型：
--
作者：
Yang M;He RL;Benovic JL;Ye RD
已知β-抑制蛋白通过与其下游效应物的相互作用来调节G蛋白信号传导。在此，我们报道了β-arrestin 1在转染细胞中与G蛋白β1γ2亚基结合，纯化的β-arrestin 1与体外翻译的Gβ1γ2相互作用。β-arrestin 1的缺失突变导致鉴定出一个区域，包括氨基酸181-280，负责其与Gβ1γ2的相互作用。β-arrestin 1的过表达促进了Gβ1γ2介导的Akt磷酸化，而小干扰RNA（siRNA）抑制内源性β-arrestin 1的表达则减弱了这种作用。通过对Akt信号调控的核因子κB（NF-κB）的研究，我们发现β-arrestin 1的过表达可显著增强Gβ1γ2介导的NF-κB蛋白核转位和NF-κ B定向荧光素酶报告基因的表达。β-arrestin 1的过表达也促进缓激肽诱导的Gβγ介导的NF-κB荧光素酶报告基因表达，其通过用特异性siRNA沉默内源性β-arrestin 1而恢复。这些结果鉴定了β-arrestin 1在结合异源三聚体G蛋白的β1γ2亚基和促进Gβγ介导的NF-κB活化的Akt信号转导中的新功能。
β-Arrestins are known to regulate G protein signaling through interactions with their downstream effectors. Here, we report that β-arrestin1 associates with the G protein β1γ2 subunits in transfected cells, and purified β-arrestin1 interacts with Gβ1γ2 derived from in vitro translation. Deletion mutagenesis of β-arrestin1 led to the identification of a region, comprising amino acids 181-280, as being responsible for its interaction with Gβ1γ2. Overexpression of β-arrestin1 facilitates Gβ1γ2-mediated Akt phosphorylation, and inhibition of endogenous β-arrestin1 expression by small interfering RNA (siRNA) diminishes this effect. Through investigation of nuclear factor κB (NF-κB), a transcription factor regulated by Akt signaling, we have found that overexpression of β-arrestin1 significantly enhances Gβ1γ2-mediated nuclear translocation of NF-κB proteins and expression of a NF-κB-directed luciferase reporter. Overexpression of β-arrestin1 also promotes bradykinin-induced, Gβγ-mediated NF-κB luciferase reporter expression, which is reverted by silencing the endogenous β-arrestin1 with a specific siRNA. These results identify novel functions of β-arrestin1 in binding to the β1γ2 subunits of heterotrimeric G proteins and promoting Gβγ-mediated Akt signaling for NF-κB activation.