Scaffold-mediated gating of Cdc42 signalling flux
Scaffold-mediated gating of Cdc42 signalling flux
复制标题
支架介导的 Cdc42 信号流门控
作者：
P. Rapali;Romain Mitteau;C. Braun;A. Massoni;Caner Ünlü;L. Bataille;Floriane Saint Arramon;S. Gygi;Derek McCusker
支架蛋白在空间上和时间上调节信号通路活性。在芽殖酵母中，支架Bem 1通过调节GTdR Cdc42而有助于极性轴的建立。虽然Bem 1的功能已经提出了不同的模型，但几乎没有直接的证据表明其潜在的机制。在这里，我们发现Bem 1直接增强了Cdc24的鸟嘌呤交换因子（GEF）活性。Bem 1还通过p21激活的激酶（PAK）Cla4增加GEF磷酸化。磷酸化消除了GEF活性的支架依赖性刺激，使Cdc24对额外的Bem 1不敏感。因此，Bem 1以可逆的方式刺激GEF活性，有助于通过Cdc42的信号传导通量。Bem 1对GTdR动力学的贡献通过体内成像被排除：在低磷酸化的cdc24突变体中，活性Cdc42在细胞极富集，而对支架刺激具有抗性的高磷酸化的cdc24突变体在极处显示活性Cdc42的缺陷。这些发现说明了支架蛋白赋予信号通路的自我调节特性。DOI：http://dx.doi.org/10.7554/eLife.25257.001网站
Scaffold proteins modulate signalling pathway activity spatially and temporally. In budding yeast, the scaffold Bem1 contributes to polarity axis establishment by regulating the GTPase Cdc42. Although different models have been proposed for Bem1 function, there is little direct evidence for an underlying mechanism. Here, we find that Bem1 directly augments the guanine exchange factor (GEF) activity of Cdc24. Bem1 also increases GEF phosphorylation by the p21-activated kinase (PAK), Cla4. Phosphorylation abrogates the scaffold-dependent stimulation of GEF activity, rendering Cdc24 insensitive to additional Bem1. Thus, Bem1 stimulates GEF activity in a reversible fashion, contributing to signalling flux through Cdc42. The contribution of Bem1 to GTPase dynamics was borne-out by in vivo imaging: active Cdc42 was enriched at the cell pole in hypophosphorylated cdc24 mutants, while hyperphosphorylated cdc24 mutants that were resistant to scaffold stimulation displayed a deficit in active Cdc42 at the pole. These findings illustrate the self-regulatory properties that scaffold proteins confer on signalling pathways. DOI: http://dx.doi.org/10.7554/eLife.25257.001
影响因子：
7.5
作者：
McCusker, Derek;Kellogg, Douglas R.
通讯作者：
Kellogg, Douglas R.
DOI：
10.1073/pnas.86.24.9976
发表时间：
1989-12-01
影响因子：
11.1
作者：
BENDER, A;PRINGLE, JR
通讯作者：
PRINGLE, JR
影响因子：
3.3
作者：
Caviston, JP;Longtine, M;Bi, E
通讯作者：
Bi, E