Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5
Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5
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DOI：
10.1016/j.molcel.2008.04.016
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发表时间：
2008-06-06
期刊：
影响因子：
16
通讯作者：
Dohlman, Henrik G.
中科院分区：
文献类型：
--
作者：
Hao, Nan;Nayak, Sujata;Dohlman, Henrik G.
细胞分化需要对各种细胞外信号的检测和响应的能力。在这里，我们研究了由单个刺激的浓度变化引起的分化开关。暴露于高剂量交配信息素的酵母细胞会经历细胞分裂的停滞。中间剂量的细胞变得伸长，并在信息素梯度的方向上分裂（趋化生长）。 fus3和kss1的信息素反应性MAP激酶都会促进细胞伸长，但只有FUS3促进了趋化的生长。尽管KSS1迅速激活并具有分级剂量反应曲线，但FUS3被缓慢地激活，并表现出较陡的剂量反应关系（超敏感性）。 FUS3活性需要支架蛋白Ste5；当废除与Ste5的结合时，FUS3的行为像KSS1一样，细胞不再对梯度或与遥远的伴侣有效地响应。我们建议支架蛋白用于调节MAP激酶的时间和剂量反应行为。
Cell differentiation requires the ability to detect and respond appropriately to a variety of extracellular signals. Here we investigate a differentiation switch induced by changes in the concentration of a single stimulus. Yeast cells exposed to high doses of mating pheromone undergo cell division arrest. Cells at intermediate doses become elongated and divide in the direction of a pheromone gradient (chemotropic growth). Either of the pheromone-responsive MAP kinases, Fus3 and Kss1, promotes cell elongation, but only Fus3 promotes chemotropic growth. Whereas Kss1 is activated rapidly and with a graded dose-response profile, Fus3 is activated slowly and exhibits a steeper dose-response relationship (ultra-sensitivity). Fus3 activity requires the scaffold protein Ste5; when binding to Ste5 is abrogated, Fus3 behaves like Kss1, and the cells no longer respond to a gradient or mate efficiently with distant partners. We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase.