A model for a network of phosphorylation-dephosphorylation cycles displaying the dynamics of dominoes and clocks
A model for a network of phosphorylation-dephosphorylation cycles displaying the dynamics of dominoes and clocks
复制标题
DOI：
10.1006/jtbi.2000.2294
复制
发表时间：
2001-05-21
影响因子：
2
通讯作者：
Goldbeter, A
中科院分区：
文献类型：
--
作者：
Gonze, D;Goldbeter, A
我们考虑了通过正向和反向调节相互作用耦合的磷酸化-去磷酸化循环网络的模型，使得在给定循环中磷酸化的蛋白质在下一个循环中激活激酶对蛋白质的磷酸化，以及蛋白质的去磷酸化。前一个循环中的磷酸酶。该网络以这样一种方式循环组织，即在最后一个循环中磷酸化的蛋白质在第一个循环中激活激酶。我们研究的动态网络中存在的前向和后向耦合，在每个周期中存在一个阈值的条件下，在蛋白质磷酸化的激酶磷酸酶的最大速率的比率的函数的量。我们表明，该系统可以显示持续的（极限环）振荡，其中每个周期的路径是连续打开和关闭，在一个序列类似的一系列多米诺骨牌的秋天。因此，该模型提供了一个生物化学的例子。显示多米诺骨牌和时钟动态的系统（Murray & Kirschner，1989）。它还表明，存在一个连续的时钟波形，其中多米诺骨牌的倒下代表了一个极限。当网络中的循环仅通过前向（正）耦合连接时，观察到双稳态，而在仅存在后向（负）耦合的情况下，系统可以显示多稳态或振荡，这取决于网络中循环的数量。抑制或激活网络中的任何激酶或磷酸酶都会使系统进入稳定的稳态，从而立即停止振荡;当激酶或磷酸酶的初始值恢复时，振荡就会恢复。因此，只要存在抑制剂，系统在极限环上的进展就可以暂时停止，就像多米诺骨牌一样。这些结果表明，真核细胞周期，由磷酸化-脱磷酸化反应的网络，其中细胞周期蛋白依赖性激酶的负控制起着突出的作用，表现为一个限制周期振荡器阻碍抑制剂的存在。我们对比的情况下，多米诺骨牌般的过渡序列构成的时钟的情况下，过渡序列是被动耦合到一个生化振荡器作为一个独立的时钟操作。(C)北京：科学出版社.
We consider a mo del for a network of phosphorylation-dephosphorylation cycles coupled through forward and backward regulatory interactions, such that a protein phosphorylated in a given cycle activates the phosphorylation of a protein by a kinase in the next cycle as well as the dephosphorylation of a protein by a phosphatase in a preceding cycle. The network is cyclically organized in such a way that the protein phosphorylated in the last cycle activates the kinase in the first cycle. We study the dynamics of the network in the presence of both forward and backward coupling, in conditions where a threshold exists in each cycle in the amount of protein phosphorylated as a function of the ratio of kinase to phosphatase maximum rates. We show that this system can display sustained (limit-cycle) oscillations in which each cycle in the pathway is successively turned on and off, in a sequence resembling the fall of a series of dominoes. The model thus provides an example of a biochemical. system displaying the dynamics of dominoes and clocks (Murray & Kirschner, 1989). It also shows that a continuum of clock waveforms exists of which the fall of dominoes represents a limit. When the cycles in the network are linked through only forward (positive) coupling, bistability is observed, while in the presence of only backward (negative) coupling, the system can display multistability or oscillations, depending on the number of cycles in the network. Inhibition or activation of any kinase or phosphatase in the network immediately stops the oscillations by bringing the system into a stable steady state; oscillations resume when the initial value of the kinase or phosphatase rate is restored. The progression of the system on the limit cycle can thus be temporarily halted as long as an inhibitor is present, much as when a domino is held in place. These results suggest that the eukaryotic cell cycle, governed by a network of phosphorylation-dephbsphorylation reactions in which the negative control of cyclin-dependent kinases plays a prominent role, behaves as a limit-cycle oscillator impeded in the presence of inhibitors. We contrast the case where the sequence of domino-like transitions constitutes the clock with the case where the sequence of transitions is passively coupled to a biochemical oscillator operating as an independent clock. (C) 2001 Academic Press.