Zaman Shadia, Lippman Soyeon I, Schneper Lisa, Slonim Noam, Broach James R
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Mol Syst Biol. 2009;5:245. doi: 10.1038/msb.2009.2. Epub 2009 Feb 17.
Addition of glucose to yeast cells increases their growth rate and results in a massive restructuring of their transcriptional output. We have used microarray analysis in conjunction with conditional mutations to obtain a systems view of the signaling network responsible for glucose-induced transcriptional changes. We found that several well-studied signaling pathways-such as Snf1 and Rgt-are responsible for specialized but limited responses to glucose. However, 90% of the glucose-induced changes can be recapitulated by the activation of protein kinase A (PKA) or by the induction of PKB (Sch9). Blocking signaling through Sch9 does not interfere with the glucose response, whereas blocking signaling through PKA does. We conclude that both Sch9 and PKA regulate a massive, nutrient-responsive transcriptional program promoting growth, but that they do so in response to different nutritional inputs. Moreover, activating PKA completely recapitulates the transcriptional growth program in the absence of any increase in growth or metabolism, demonstrating that activation of the growth program results solely from the cell's perception of its nutritional status.
向酵母细胞中添加葡萄糖可提高其生长速率，并导致其转录输出发生大规模重组。我们结合条件突变使用微阵列分析，以获得负责葡萄糖诱导转录变化的信号网络的系统视图。我们发现，几个经过充分研究的信号通路，如Snf1和Rgt，负责对葡萄糖的特定但有限的反应。然而，90%的葡萄糖诱导变化可以通过蛋白激酶A（PKA）的激活或PKB（Sch9）的诱导来重现。通过Sch9阻断信号传导不会干扰葡萄糖反应，而通过PKA阻断信号传导则会。我们得出结论，Sch9和PKA都调节促进生长的大规模营养响应转录程序，但它们是对不同的营养输入做出反应。此外，如果没有任何生长或代谢的增加，激活PKA完全可以重现转录生长程序，这表明生长程序的激活完全是由于细胞对其营养状态的感知。
