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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Crosstalk between cAMP-PKA and MAP kinase pathways is a key regulatory design necessary to regulate FLO11 expression
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Crosstalk between cAMP-PKA and MAP kinase pathways is a key regulatory design necessary to regulate FLO11 expression

机译：cAMP-PKA和MAP激酶途径之间的串扰是调节FLO11表达所必需的关键调节设计

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Signal transduction pathways crosstalk with one another and play a central role in regulation of cellular events. Crosstalk brings complexity to the system, and hence, a systematic analysis of these crosstalks helps in relating the signaling network structure to its function. Here, we present a modular steady state approach to quantify the network comprising of cAMP-PKA and MAP kinase pathways involved in the regulation of FLO11, a gene which is required for pseudohyphae growth in Saccharomyces cerevisiae under nitrogen starvation. These two pathways crosstalk by converging on the same target, i.e., FLO11 and through Ras2p, an upstream activator of both cAMP and MAPK pathway. Analysis of crosstalk at the gene level revealed that cAM-P-PKA and MAPK pathways are indispensable to FLO11 expression. The dose response was highly sensitive and primarily controlled by cAMP-PKA pathway. We demonstrate that the highly sensitive response in the cAMP-PKA pathway was due to crosstalk and inhibitor ultrsensitivity, key regulatory designs present at the downstream of cAMP-PKA pathway. The analysis of the role of Ras2p in the crosstalk between the cAMP-PKA and MAPK pathways indicated that crosstalk essentially helped in amplification of the Gpa2p signal, another. upstream activator of the cAMP-PKA pathway. However, the effect of crosstalk due to Ras2p on FLO11 expression was minimal under normal activation levels of Ras2p. Whereas, the crosstalk itself can bring about FLO11 expression under the hyperactivated Ras2p conditions thereby eliminating the requirement for the other activator Gpa2p. We also observed the presence of system level properties such as amplification, inhibitor ultrasensirvity and bistability, which can be attributed to the regulatory design present in the FLO11 expression system. These system level properties might help the organism to respond to varying nutritional status. (c) 2006 Elsevier B.V. All rights reserved.
机译：信号转导途径相互串扰，并在调节细胞事件中起核心作用。串扰给系统带来了复杂性，因此，对这些串扰的系统分析有助于使信令网络结构与其功能相关。在这里，我们提出了一种模块化的稳态方法来量化网络，该网络包括参与调控FLO11的cAMP-PKA和MAP激酶途径，FLO11是酿酒酵母在氮饥饿下假菌丝生长所需的基因。这两个途径通过聚集在同一个靶标即FLO11上并通过Ras2p（cAMP和MAPK途径的上游激活剂）相互干扰。在基因水平上的串扰分析显示，cAM-P-PKA和MAPK途径对于FLO11表达必不可少。剂量反应高度敏感，主要受cAMP-PKA途径控制。我们证明，在cAMP-PKA途径中的高度敏感反应是由于串扰和抑制剂的超敏性，这是cAMP-PKA途径下游存在的关键调控设计。对Ras2p在cAMP-PKA和MAPK途径之间的串扰中的作用的分析表明，串扰实质上有助于放大Gpa2p信号（另一个）。 cAMP-PKA途径的上游激活剂。但是，在正常Ras2p激活水平下，由Ras2p引起的串扰对FLO11表达的影响极小。而串扰本身可以在高度激活的Ras2p条件下引起FLO11表达，从而消除了对其他激活剂Gpa2p的需求。我们还观察到了系统水平特性的存在，例如扩增，抑制剂超敏性和双稳性，这可以归因于FLO11表达系统中存在的调控设计。这些系统水平的特性可能有助于有机体对各种营养状况做出反应。 （c）2006 Elsevier B.V.保留所有权利。

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