Relevance of the kinetic equilibrium of forces to the control of the cell cycle by Ras proteins
Relevance of the kinetic equilibrium of forces to the control of the cell cycle by Ras proteins
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DOI：
10.1515/bc.2004.006
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Becker, EW
中科院分区：
文献类型：
--
作者：
Becker, EW
在高等生物中，在交换因子的参与下，GTR取代与Ras蛋白结合的GDP是细胞分裂起始的重要步骤。Ras-GTP激活激酶和其他效应物，将信号传递到细胞核和细胞骨架。Ras的活性状态通过结合的GTP在活化蛋白（GAP）的协助下水解而终止。这些调控事件的知识是基于大量的实验数据，但他们的解释的许多方面仍然存在争议。这里假设，当两个伴侣结合时释放的自由能的很大一部分储存在“力的动力学平衡”（KEF）中，并用于促进与第三伴侣的分离。Raf激酶的活化主要解释为Ras-GTP对激酶催化区磷酸转移的变构效应。提出了一种机制，修改GAP的Ras-GTP，这被认为是一个先决条件，为众所周知的Ras和Rho依赖的信号通路之间的串扰。细胞通过满足KEF的要求，设法减少激活障碍，从而显著加速调节事件和其他复杂的生物反应序列。
In higher organisms, the replacement of GDP bound to Ras proteins with GTR under the participation of an exchange factor, is an important step in the initiation of cell division. Ras-GTP activates kinases and other effectors, which pass signals to the cell nucleus and to the cytoskeleton. The active state of Ras is terminated by hydrolysis of the bound GTP with the assistance of an activating protein (GAP). Knowledge of these regulatory events is based on extensive experimental data, but many aspects of their interpretation are still controversial. It is assumed here that a significant part of the free energy released when two partners associate is stored in a 'kinetic equilibrium of forces' (KEF), and used to facilitate the separation from a third partner. The activation of the Raf kinase is explained primarily in terms of an allosteric effect of Ras-GTP on the phosphate transfer in the catalytic region of the kinase. A mechanism is proposed for the modification of GAP by Ras-GTP, which is believed to be a prerequisite for the well-known crosstalk between the Ras- and Rho-dependent signalling pathways. The cell, by meeting the requirements for KEF, manages to reduce activation barriers, thus significantly accelerating the regulatory events and other complex biological reaction sequences.