Department of Biochemistry and Biophysics, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, United States of America.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
PLoS One. 2020 Mar 11;15(3):e0230246. doi: 10.1371/journal.pone.0230246. eCollection 2020.
Cells respond to changes in environmental conditions by activating signal transduction pathways and gene expression programs. Here we present a dataset to explore the relationship between environmental stresses, kinases, and global gene expression in yeast. We subjected 28 drug-sensitive kinase mutants to 10 environmental conditions in the presence of inhibitor and performed mRNA deep sequencing. With these data, we reconstructed canonical stress pathways and identified examples of crosstalk among pathways. The data also implicated numerous kinases in novel environment-specific roles. However, rather than regulating dedicated sets of target genes, individual kinases tuned the magnitude of induction of the environmental stress response (ESR)-a gene expression signature shared across the set of perturbations-in environment-specific ways. This suggests that the ESR integrates inputs from multiple sensory kinases to modulate gene expression and growth control. As an example, we provide experimental evidence that the high osmolarity glycerol pathway is an upstream negative regulator of protein kinase A, a known inhibitor of the ESR. These results elaborate the central axis of cellular stress response signaling.
细胞通过激活信号转导途径和基因表达程序来响应环境条件的变化。在这里，我们提供了一个数据集，以探讨酵母中环境应激、激酶和全局基因表达之间的关系。我们将 28 种药物敏感型激酶突变体在抑制剂存在的情况下置于 10 种环境条件下，并进行了 mRNA 深度测序。利用这些数据，我们重建了典型的应激途径，并确定了途径之间相互作用的例子。这些数据还表明，许多激酶在新的环境特异性作用中具有重要作用。然而，单个激酶并没有调节特定的靶基因，而是以环境特异性的方式调节环境应激反应（ESR）——一组扰动共有的基因表达特征的诱导幅度。这表明 ESR 整合了来自多个感觉激酶的输入，以调节基因表达和生长控制。例如，我们提供了实验证据表明，高渗透压甘油途径是蛋白激酶 A 的上游负调控因子，蛋白激酶 A 是 ESR 的已知抑制剂。这些结果详细阐述了细胞应激反应信号的中心轴。
