Analysis of the thresholds for transcriptional activation by the yeast MAP kinases Fus3 and Kss1.
Analysis of the thresholds for transcriptional activation by the yeast MAP kinases Fus3 and Kss1.
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DOI：
10.1091/mbc.e17-10-0578
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发表时间：
2018-03-01
影响因子：
3.3
通讯作者：
Pryciak PM
中科院分区：
文献类型：
--
作者：
Winters MJ;Pryciak PM
出芽酵母信息素反应通路中的信号激活两种不同的MAP激酶（MAPKs）， Fus3和Kss1。单独的MAPK都可以介导信息素诱导的转录，但在野生型细胞中，每种MAPK对转录输出的贡献程度尚不清楚。在这里，我们报告了转录反映了活性与非活性MAPK的比例，而不仅仅是活性MAPK的水平。对于Kss1，大多数MAPK分子必须转化为活性形式，而对于Fus3，只有一小部分必须被激活。这些不同的激活阈值反映了每个MAPK的两种相反的作用，其中非活性形式抑制转录，而活性形式促进转录。此外，来自Fus3的负反馈限制了Kss1的激活，因此它在野生型细胞中不能达到所需的阈值，而只有在缺乏Fus3的细胞中过度激活时才能达到所需的阈值。结果表明，正常的转录反应涉及两个mapk的不对称贡献，其中信息素信号减少了Kss1的负面影响，而增加了Fus3的积极影响。这些发现揭示了这些mapk之间新的功能差异，并有助于阐明抑制功能如何在信息素和丝化途径中塑造积极的通路输出。
Signaling in the pheromone response pathway of budding yeast activates two distinct MAP kinases (MAPKs), Fus3 and Kss1. Either MAPK alone can mediate pheromone-induced transcription, but it has been unclear to what degree each one contributes to transcriptional output in wild-type cells. Here, we report that transcription reflects the ratio of active to inactive MAPK, and not simply the level of active MAPK. For Kss1 the majority of MAPK molecules must be converted to the active form, whereas for Fus3 only a small minority must be activated. These different activation thresholds reflect two opposing effects of each MAPK, in which the inactive forms inhibit transcription, whereas the active forms promote transcription. Moreover, negative feedback from Fus3 limits activation of Kss1 so that it does not meet its required threshold in wild-type cells but does so only when hyperactivated in cells lacking Fus3. The results suggest that the normal transcriptional response involves asymmetric contributions from the two MAPKs, in which pheromone signaling reduces the negative effect of Kss1 while increasing the positive effect of Fus3. These findings reveal new functional distinctions between these MAPKs, and help illuminate how inhibitory functions shape positive pathway outputs in both pheromone and filamentation pathways.