Scaffold proteins confer diverse regulatory properties to protein kinase cascades
Scaffold proteins confer diverse regulatory properties to protein kinase cascades
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DOI：
10.1073/pnas.0706311104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Chakraborty, Arup K.
中科院分区：
文献类型：
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作者：
Locasale, Jason W.;Shaw, Andrey S.;Chakraborty, Arup K.
多个信号蛋白通过支架蛋白组装成一个复合体，指导着许多细胞决策。尽管最近取得了进展，但支配脚手架功能的首要原则还没有得到很好的理解。我们利用动力学蒙特卡罗模拟进行了一项计算研究，以了解在不同的生理条件下，支架上的激酶的空间定位如何调节信号。我们的研究确定了支架蛋白的调节特性，使它们能够在不同的生物环境中放大和衰减传入信号。这些特性不是由已确定的前地带或组合抑制效应引起的。这些结果给看似自相矛盾的观察带来了一致性，并表明细胞已经进化出设计规则，使支架蛋白能够调节广泛不同的细胞功能。
The assembly of multiple signaling proteins into a complex by a scaffold protein guides many cellular decisions. Despite recent advances, the overarching principles that govern scaffold function are not well understood. We carried out a computational study using kinetic Monte Carlo simulations to understand how spatial localization of kinases on a scaffold may regulate signaling under different physiological conditions. Our studies identify regulatory properties of scaffold proteins that allow them to both amplify and attenuate incoming signals in different biological contexts. These properties are not caused by the well established prozone or combinatorial inhibition effect. These results bring coherence to seemingly paradoxical observations and suggest that cells have evolved design rules that enable scaffold proteins to regulate widely disparate cellular functions.