Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS Genet. 2012 Jan;8(1):e1002437. doi: 10.1371/journal.pgen.1002437. Epub 2012 Jan 5.
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.
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，这些信号会引发细胞变化，但这些变化是相互排斥的，因此必须由反应细胞进行协调。在酵母酿酒酵母中，高渗应激和交配信息素分别启动信号级联反应，最终都终止于 MAP 激酶 Hog1 和 Fus3。尽管这些途径共享成分，但它们是由不同的输入引发的，并产生不同的细胞行为。为了理解这些反应是如何协调的，我们在高渗条件下监测了信息素反应。我们表明，高渗应激至少通过三种方式限制信息素信号。首先，应激会延迟信息素诱导基因的表达。其次，应激会促进蛋白激酶 Rck2 的磷酸化，从而抑制信息素诱导的蛋白质翻译。第三，应激会促进共享途径成分 Ste50 的磷酸化，从而抑制信息素诱导的 MAPK 激活。尽管所有三种机制都依赖于渗透压的增加，但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通过协调作用作用于多个途径成分来推迟对竞争分化信号的反应。
