環(huán)AMP（分子生物學中被發(fā)現最早,、被研究最多的信號分子之一）被廣泛認為是專注于細菌中的碳代謝?，F在,，Terence Hwa及同事揭示了該分子的一個涉及范圍要廣得多的生理作用：環(huán)AMP信號作用響應于全面代謝需求（如包括氮和磷）協(xié)調整個基因組的資源分配。為了實現對分子生物學教科書的這一改寫,，他們采用了一個被稱為“定量現象學”的不同尋常的自上而下的方法,，該方法也有可能應用到其他信號通道（如那些在哺乳動物細胞中產生癌癥的信號通道）的系統(tǒng)生物學研究中。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
