环AMP（分子生物学中被发现最早、被研究最多的信号分子之一）被广泛认为是专注于细菌中的碳代谢。现在，Terence Hwa及同事揭示了该分子的一个涉及范围要广得多的生理作用：环AMP信号作用响应于全面代谢需求（如包括氮和磷）协调整个基因组的资源分配。为了实现对分子生物学教科书的这一改写，他们采用了一个被称为“定量现象学”的不同寻常的自上而下的方法，该方法也有可能应用到其他信号通道（如那些在哺乳动物细胞中产生癌症的信号通道）的系统生物学研究中。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi: 10.1038/nature12446
Coordination of bacterial proteome with metabolism by cyclic AMP signalling
Conghui You, Hiroyuki Okano, Sheng Hui, Zhongge Zhang, Minsu Kim, Carl W. Gunderson, Yi-Ping Wang, Peter Lenz, Dalai Yan & Terence Hwa
The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
