Positional information generated by spatially distributed signaling cascades.
Positional information generated by spatially distributed signaling cascades.
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DOI：
10.1371/journal.pcbi.1000330
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发表时间：
2009-03
影响因子：
4.3
通讯作者：
Kholodenko BN
中科院分区：
文献类型：
--
作者：
Muñoz-García J;Neufeld Z;Kholodenko BN
蛋白质修饰级联的时间和稳态行为已被广泛研究，但对信号传播的空间方面知之甚少。我们以前已经表明，相对的酶，如激酶和磷酸酶的空间分离，创建信号活性梯度。在这里，我们展示了在什么条件下信号在空间中停滞或通过空间分布的信号级联稳健地传播。稳健的信号传播导致具有长平台的活动梯度，其在连续的空间位置处突然衰减。我们推导出一个近似的解析解，涉及的最大振幅和传播长度的每个激活配置文件的级联水平，蛋白质扩散率，和相对的酶活性的比率。空间信号传播的控制似乎是非常不同的空间均匀级联的瞬态时间响应的控制。对于空间分布的级联，其中激活和失活酶远离饱和操作，相反的酶活性的比率被证明是控制信号传播的关键参数。稳健信号传播的信号梯度特征是一种模式形成机制，该机制为多个细胞过程产生精确的空间指导，并将有关细胞大小的信息传递到细胞核。活细胞检测环境线索，并利用蛋白质修饰周期的信号级联将信号传播到细胞内部。一个循环由一对相反的酶组成，控制蛋白质的激活和失活，其中活性形式将信号传递到下一个级联水平。细胞和发育生物学中的一个关键挑战是了解这些级联如何在长距离上传递信号，以及空间信息如何在这些信号中编码。随着先进成像技术的出现，人们对理解细胞和组织中的信号传播产生了兴趣。基于一个简单的级联模型，我们确定信号传播的条件，并显示如何传播信号产生的空间模式，可以提供各种细胞过程的位置信息。
The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propagate through spatially distributed signaling cascades. Robust signal propagation results in activity gradients with long plateaus, which abruptly decay at successive spatial locations. We derive an approximate analytical solution that relates the maximal amplitude and propagation length of each activation profile with the cascade level, protein diffusivity, and the ratio of the opposing enzyme activities. The control of the spatial signal propagation appears to be very different from the control of transient temporal responses for spatially homogenous cascades. For spatially distributed cascades where activating and deactivating enzymes operate far from saturation, the ratio of the opposing enzyme activities is shown to be a key parameter controlling signal propagation. The signaling gradients characteristic for robust signal propagation exemplify a pattern formation mechanism that generates precise spatial guidance for multiple cellular processes and conveys information about the cell size to the nucleus. Living cells detect environmental cues and propagate signals into the cell interior employing signaling cascades of protein modification cycles. A cycle consists of a pair of opposing enzymes controlling the activation and deactivation of a protein, where the active form transmits the signal to the next cascade level. A crucial challenge in cell and developmental biology is to understand how these cascades convey signals over large distances and how spatial information is encoded in these signals. With the advent of advanced imaging techniques, there has been emerging interest in understanding signal propagation in cells and tissues. Based on a simple cascade model, we determine the conditions for signal propagation and show how propagating signals generate spatial patterns that can provide positional information for various cellular processes.
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影响因子：
1.7
作者：
Corless, RM;Gonnet, GH;Knuth, DE
通讯作者：
Knuth, DE
影响因子：
5.4
作者：
Blüthgen, N;Bruggeman, FJ;Kholodenko, BN
通讯作者：
Kholodenko, BN
影响因子：
16
作者：
Heinrich, R;Neel, BG;Rapoport, TA
通讯作者：
Rapoport, TA
影响因子：
64.8
作者：
Fuller, Brian G.;Lampson, Michael A.;Kapoor, Tarun M.
通讯作者：
Kapoor, Tarun M.
DOI：
10.1111/j.1432-1033.1992.tb17402.x
发表时间：
1992-11-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
KHOLODENKO, BN;LYUBAREV, AE;KURGANOV, BI
通讯作者：
KURGANOV, BI