Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks
Kinetic insulation as an effective mechanism for achieving pathway specificity in intracellular signaling networks
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DOI：
10.1073/pnas.0703894104
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发表时间：
2007-10-09
影响因子：
11.1
通讯作者：
Elston, Timothy C.
中科院分区：
文献类型：
--
作者：
Behar, Marcelo;Dohlman, Henrik G.;Elston, Timothy C.
具有共同成分的细胞内信号通路常常引起不同的生理反应。在大多数情况下，负责这种信号特异性的生化机制仍然知之甚少。蛋白质支架和交叉抑制已被提出作为防止不必要的串扰的策略。在这里，我们报告了一种被称为“动能绝缘”的信号特异性机制。在这种方法中，信号根据其时间分布有选择地通过适当的途径传输。特别是，我们展示了如何设计共同组件下游的路径架构，以有效地将瞬态信号与随时间缓慢增加的信号分离开来。此外，我们证明了上游信号蛋白可以产生适当的输入到共同的途径成分，而不管外部刺激的时间分布。我们的研究结果表明，多层次的信号级联可能已经进化到调节通路活动的时间分布，以便刺激信息可以有效地编码和传输，同时确保信号的特异性。
Intracellular signaling pathways that share common components often elicit distinct physiological responses. In most cases, the biochemical mechanisms responsible for this signal specificity remain poorly understood. Protein scaffolds and cross-inhibition have been proposed as strategies to prevent unwanted cross-talk. Here, we report a mechanism for signal specificity termed "kinetic insulation." In this approach signals are selectively transmitted through the appropriate pathway based on their temporal profile. In particular, we demonstrate how pathway architectures downstream of a common component can be designed to efficiently separate transient signals from signals that increase slowly over time. Furthermore, we demonstrate that upstream signaling proteins can generate the appropriate input to the common pathway component regardless of the temporal profile of the external stimulus. Our results suggest that multilevel signaling cascades may have evolved to modulate the temporal profile of pathway activity so that stimulus information can be efficiently encoded and transmitted while ensuring signal specificity.