Checkpoints in a yeast differentiation pathway coordinate signaling during hyperosmotic stress.
Checkpoints in a yeast differentiation pathway coordinate signaling during hyperosmotic stress.
复制标题
DOI：
10.1371/journal.pgen.1002437
复制
发表时间：
2012-01
期刊：
影响因子：
4.5
通讯作者：
Dohlman HG
中科院分区：
文献类型：
--
作者：
Nagiec MJ;Dohlman HG
所有真核生物都有能力检测和响应环境和激素信号。在许多情况下，这些信号引起的细胞变化是不相容的，因此必须由响应细胞协调。在酿酒酵母中，高渗胁迫和交配信息素启动信号级联，每个终止于MAP激酶，Hog1和Fus3，分别。尽管共享组件，但这些途径由不同的输入启动，并产生不同的细胞行为。为了了解这些反应是如何协调的，我们在高渗条件下监测信息素的反应。我们表明，高渗胁迫限制信息素信号至少在三个方面。首先，压力延迟了信息素诱导基因的表达。第二，应激促进蛋白激酶Rck2的磷酸化，从而抑制信息素诱导的蛋白质翻译。第三，压力促进了一个共享的途径组件，Ste50的磷酸化，从而抑制信息素诱导的MAPK激活。而所有这三种机制都依赖于渗透压的增加，只有磷酸化事件需要Hog1。这些发现揭示了环境应激信号如何能够通过以协调的方式作用于多个途径组分来推迟对竞争性分化信号的响应。所有的细胞都可以检测到并响应环境中的信号。正确的生长和分化需要准确解释这些信号的能力。此外，细胞在面对竞争信号时必须优先考虑反应。然而，控制信号优先化的分子机制知之甚少。为了解决这个问题，我们研究了两个信号通路的遗传模式生物芽殖酵母。具体来说，我们集中在信息素交配（分化）途径和高渗透压甘油（应激反应）途径。这些通路对每个刺激的反应不同，尽管共享通路组件。我们发现，细胞必须先适应压力，然后才能交配。在早期，应激反应交叉抑制和抑制信息素反应，以暂停交配分化。一旦细胞适应，应激反应结束，分化程序恢复。所有调节细胞命运决定的信号通路都在不同程度上相互关联。我们的研究强调了适当的信号协调在细胞命运决定中的重要性，并揭示了复杂信号网络中控制信号协调的新机制。
All eukaryotes have the ability to detect and respond to environmental and hormonal signals. In many cases these signals evoke cellular changes that are incompatible and must therefore be orchestrated by the responding cell. In the yeast Saccharomyces cerevisiae, hyperosmotic stress and mating pheromones initiate signaling cascades that each terminate with a MAP kinase, Hog1 and Fus3, respectively. Despite sharing components, these pathways are initiated by distinct inputs and produce distinct cellular behaviors. To understand how these responses are coordinated, we monitored the pheromone response during hyperosmotic conditions. We show that hyperosmotic stress limits pheromone signaling in at least three ways. First, stress delays the expression of pheromone-induced genes. Second, stress promotes the phosphorylation of a protein kinase, Rck2, and thereby inhibits pheromone-induced protein translation. Third, stress promotes the phosphorylation of a shared pathway component, Ste50, and thereby dampens pheromone-induced MAPK activation. Whereas all three mechanisms are dependent on an increase in osmolarity, only the phosphorylation events require Hog1. These findings reveal how an environmental stress signal is able to postpone responsiveness to a competing differentiation signal, by acting on multiple pathway components, in a coordinated manner. All cells can detect and respond to signals in their environment. The ability to interpret these signals with accuracy is needed for proper growth and differentiation. Moreover, cells must prioritize responses when confronted with competing signals. However the molecular mechanisms that govern signal prioritization are poorly understood. To address this question, we studied two signaling pathways in the genetic model organism budding yeast. Specifically we focused on the pheromone mating (differentiation) pathway and the high osmolarity glycerol (stress response) pathway. These pathways respond differently to each stimulus despite sharing pathway components. We find that cells must first adapt to stress before they can mate. At early times, the stress response cross-inhibits and dampens the pheromone response to suspend mating differentiation. Once cells adapt, the stress response ends and the differentiation program resumes. All signaling pathways that regulate cell fate decisions are interconnected to varying degrees. Our study highlights the importance of proper signal coordination in cell fate decisions, and it reveals new mechanisms that govern signal coordination within complex signaling networks.
登录
查看更多内容
DOI：
10.1016/j.cub.2008.09.027
发表时间：
2008-11-11
期刊：
Current biology : CB
影响因子：
--
作者：
Hilioti Z;Sabbagh W Jr;Paliwal S;Bergmann A;Goncalves MD;Bardwell L;Levchenko A
通讯作者：
Levchenko A
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
10.5
作者：
CAIRNS, BR;RAMER, SW;KORNBERG, RD
通讯作者：
KORNBERG, RD
影响因子：
5.3
作者：
Bilsland-Marchesan, E;Ariño, J;Posas, F
通讯作者：
Posas, F
影响因子：
9.2
作者：
Hao, Nan;Behar, Marcelo;Dohlman, Henrik G.
通讯作者：
Dohlman, Henrik G.