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A Highlights from MBoC Selection: Combined computational and experimental analysis reveals mitogen-activated protein kinase–mediated feedback phosphorylation as a mechanism for signaling specificity

机译:MBoC选择的亮点:组合的计算和实验分析表明促分裂原活化的蛋白激酶介导的反馈磷酸化是信号传导特异性的机制

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摘要

Different environmental stimuli often use the same set of signaling proteins to achieve very different physiological outcomes. The mating and invasive growth pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7 activation of the MAP kinase Fus3, invasive growth requires activation of the alternate MAP kinase Kss1. To determine how MAP kinase specificity is achieved, we used a series of mathematical models to quantitatively characterize pheromone-stimulated kinase activation. In accordance with the computational analysis, MAP kinase feedback phosphorylation of Ste7 results in diminished activation of Kss1, but not Fus3. These findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity.
机译:不同的环境刺激通常使用同一组信号蛋白来实现截然不同的生理结果。酵母中的交配和侵袭性生长途径均采用丝裂原激活蛋白(MAP)激酶级联反应,其中包括Ste20,Ste11和Ste7。适当的交配需要MAP激酶Fus3的Ste7激活,而侵入性生长则需要替代的MAP激酶Kss1的激活。为了确定如何实现MAP激酶特异性,我们使用了一系列数学模型来定量表征信息素刺激的激酶激活。根据计算分析,Ste7的MAP激酶反馈磷酸化导致Kss1激活减少,而Fus3激活减少。这些发现揭示了共同途径组分的反馈磷酸化如何通过共同激活剂的反馈磷酸化来限制竞争性MAP激酶的活性,从而促进信号保真度。

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