Dose-Duration Reciprocity for G protein activation: Modulation of kinase to substrate ratio alters cell signaling.

Dose-Duration Reciprocity for G protein activation: Modulation of kinase to substrate ratio alters cell signaling.
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DOI:
10.1371/journal.pone.0190000
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Jones AM
Jones AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liao KL;Melvin CE;Sozzani R;Jones RD;Elston TC;Jones AM

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在动物细胞中,异源三聚体 G 蛋白信号传导通常在系统的同源信号超过阈值时发生,而在植物细胞中,至少一种信号(D-葡萄糖)的数量和暴露时间都用于激活。这种不寻常的信号特性称为“剂量持续时间互惠”,首先在拟南芥遗传模型中得到阐明,是通过一种复合物实现的,该复合物由 7 次跨膜 G 信号调节蛋白 (RGS) (AtRGS1)、结合和水解核苷酸的 Gα 亚基、Gβγ 二聚体和三个不含赖氨酸 (WNK) 的激酶组成。 D-葡萄糖是盐和病原体衍生分子模式等多种信号之一,通过该蛋白质复合物发挥作用,通过 AtRGS1 的 WNK 激酶转磷酸化激活 G 蛋白信号传导。由于 WNK 激酶竞争相同的底物 AtRGS1,因此我们假设激活对 AtRGS1 的量敏感,并且 AtRGS1 池的调节会影响对兴奋剂的反应。数学模拟表明,AtRGS1 与激酶的比例会影响系统对 D-葡萄糖的敏感性,因此说明了细胞 AtRGS1 水平的调节如何成为改变信号诱导激活的一种手段。 AtRGS1 水平在模拟生理条件的测试条件下发生变化,因此,我们提出了一种以前未知的机制,植物通过该机制对其环境变化做出反应。
In animal cells, activation of heterotrimeric G protein signaling generally occurs when the system’s cognate signal exceeds a threshold, whereas in plant cells, both the amount and the exposure time of at least one signal, D-glucose, are used toward activation. This unusual signaling property called Dose-Duration Reciprocity, first elucidated in the genetic model Arabidopsis thaliana, is achieved by a complex that is comprised of a 7-transmembrane REGULATOR OF G SIGNALING (RGS) protein (AtRGS1), a Gα subunit that binds and hydrolyzes nucleotide, a Gβγ dimer, and three WITH NO LYSINE (WNK) kinases. D-glucose is one of several signals such as salt and pathogen-derived molecular patterns that operates through this protein complex to activate G protein signaling by WNK kinase transphosphorylation of AtRGS1. Because WNK kinases compete for the same substrate, AtRGS1, we hypothesize that activation is sensitive to the AtRGS1 amount and that modulation of the AtRGS1 pool affects the response to the stimulant. Mathematical simulation revealed that the ratio of AtRGS1 to the kinase affects system sensitivity to D-glucose, and therefore illustrates how modulation of the cellular AtRGS1 level is a means to change signal-induced activation. AtRGS1 levels change under tested conditions that mimic physiological conditions therefore, we propose a previously-unknown mechanism by which plants react to changes in their environment.
植物王国中的异三聚体G蛋白信号传导。
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