The Dark Side of Cell Signaling: Positive Roles for Negative Regulators.
The Dark Side of Cell Signaling: Positive Roles for Negative Regulators.
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DOI：
10.1016/j.cell.2016.02.047
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发表时间：
2016-03-10
期刊：
影响因子：
64.5
通讯作者：
Kiyatkin A
中科院分区：
文献类型：
--
作者：
Lemmon MA;Freed DM;Schlessinger J;Kiyatkin A
细胞信号传导主要通过分析对刺激的积极反应来控制。信号激活通过负调节因子来平衡，负调节因子通常被认为是终止信号传导。然而，许多此类调节因子不仅仅产生负面影响，而且在增强细胞信号传导控制方面发挥着重要作用。考虑到选定细胞表面受体下游的反应，我们讨论了受体内化如何影响信号传导特异性，以及快速的激酶/磷酸酶和 GTP/GDP 循环如何提高反应性并允许受体信号传导的动力学校对。我们强调正信号和负信号之间区别的模糊，将信号终止重新定义为对新细胞状态的类似开关转变的响应。
Cell signaling is dominated by analyzing positive responses to stimuli. Signal activation is balanced by negative regulators that are generally considered to terminate signaling. Rather than exerting only negative effects, however, many such regulators play important roles in enhancing cell-signaling control. Considering responses downstream of selected cell-surface receptors, we discuss how receptor internalization affects signaling specificity and how rapid kinase/phosphatase and GTP/GDP cycles increase responsiveness and allow kinetic proofreading in receptor signaling. We highlight the blurring of distinctions between positive and negative signals, recasting signal termination as the response to a switch-like transition into a new cellular state.