Hysteretic and graded responses in bacterial two-component signal transduction
Hysteretic and graded responses in bacterial two-component signal transduction
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DOI：
10.1111/j.1365-2958.2008.06221.x
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Savageau, Michael A.
中科院分区：
文献类型：
--
作者：
Igoshin, Oleg A.;Alves, Rui;Savageau, Michael A.
细菌双组分系统（TCS）是调节全球环境变化响应的关键信号转导网络。环境信号可以调节传感器激酶（SK）的磷酸化状态。磷酸化的SK将磷酸转移到其同源反应调节因子（RR），其引起对信号的生理反应。通常，SK是双功能的，并且当未磷酸化时，它也能够使RR去磷酸化。磷酸酶活性也可以通过环境信号调节。以EnvZ/OmpR系统为例，构建了数学模型，考察了网络的稳态和动力学性质。数学模型表明，TCS可以显示出一个给定的参数值范围内的行为，如果非磷酸化的SK和RR形成一个死端复合物，防止SK自磷酸化。此外，对于双稳态存在的RR的主要去磷酸化通量必须不依赖于非磷酸化SK。结构建模和已发表的亲和性研究表明，非磷酸化SK EnvZ和RR OmpR形成一个死端复合物。然而，双稳态是不可能的，因为类似于P的OmpR的去磷酸化主要由未磷酸化的EnvZ完成。这种潜在的双稳态在设计的EnvZ/OmpR网络和其他TCS的影响进行了讨论。
Bacterial two-component systems (TCS) are key signal transduction networks regulating global responses to environmental change. Environmental signals may modulate the phosphorylation state of sensor kinases (SK). The phosphorylated SK transfers the phosphate to its cognate response regulator (RR), which causes physiological response to the signal. Frequently, the SK is bifunctional and, when unphosphorylated, it is also capable of dephosphorylating the RR. The phosphatase activity may also be modulated by environmental signals. Using the EnvZ/OmpR system as an example, we constructed mathematical models to examine the steady-state and kinetic properties of the network. Mathematical modelling reveals that the TCS can show bistable behaviour for a given range of parameter values if unphosphorylated SK and RR form a dead-end complex that prevents SK autophosphorylation. Additionally, for bistability to exist the major dephosphorylation flux of the RR must not depend on the unphosphorylated SK. Structural modelling and published affinity studies suggest that the unphosphorylated SK EnvZ and the RR OmpR form a dead-end complex. However, bistability is not possible because the dephosphorylation of OmpR similar to P is mainly done by unphosphorylated EnvZ. The implications of this potential bistability in the design of the EnvZ/OmpR network and other TCS are discussed.