Signal processing by the HOG MAP kinase pathway

被引:192
|
作者
Hersen, Pascal [2 ,3 ,5 ]
McClean, Megan N. [1 ,3 ]
Mahadevan, L. [1 ]
Ramanathan, Sharad [3 ,4 ]
机构
[1] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] CNRS, Lab Mat & Syst Complexes, F-75205 Paris 13, France
[3] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA
[4] Bell Labs, Alcatel Lucent, Murray Hill, NJ 07974 USA
[5] Univ Paris Diderot, F-75205 Paris 13, France
关键词
bandwidth; HOG pathway; microfluidics; signal transduction;
D O I
10.1073/pnas.0710770105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Signaling pathways relay information about changes in the external environment so that cells can respond appropriately. How much information a pathway can carry depends on its bandwidth. We designed a microfluiclic device to reliably change the environment of single cells over a range of frequencies. Using this device, we measured the bandwidth of the Saccharomyces cerevisiae signaling pathway that responds to high osmolarity. This prototypical pathway, the HOG pathway, is shown to act as a low-pass filter, integrating the signal when it changes rapidly and following it faithfully when it changes more slowly. We study the dependence of the pathway's bandwidth on its architecture. We measure previously unknown bounds on all of the in vivo reaction rates acting in this pathway. We find that the two-component Ssk1 branch of this pathway is capable of fast signal integration, whereas the kinase Ste11 branch is not. Our experimental techniques can be applied to other signaling pathways, allowing the measurement of their in vivo kinetics and the quantification of their information capacity.
引用
收藏
页码:7165 / 7170
页数:6
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