Deactivation of a negative regulator: a distinct signal transduction mechanism, pronounced in Akt signaling.

Deactivation of a negative regulator: a distinct signal transduction mechanism, pronounced in Akt signaling.
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负调节因子的失活:一种独特的信号转导机制,在 Akt 信号传导中很明显。

DOI:
10.1016/j.bpj.2014.10.003
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发表时间:
2014
影响因子:
3.4
通讯作者:
Haugh,JasonM
Haugh,JasonM
中科院分区:
生物学3区
文献类型:
--
作者:
Rahman,Anisur;Haugh,JasonM

文献摘要

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Kinase cascades, in which enzymes are sequentially activated by phosphorylation, are quintessential signaling pathways. Signal transduction is not always achieved by direct activation, however. Often, kinases activate pathways by deactivation of a negative regulator; this indirect mechanism, pervasive in Akt signaling, has yet to be systematically explored. Here, we show that the indirect mechanism has properties that are distinct from direct activation. With comparable parameters, the indirect mechanism yields a broader range of sensitivity to the input, beyond saturation of regulator phosphorylation, and kinetics that become progressively slower, not faster, with increasing input strength. These properties can be integrated in network motifs to produce desired responses, as in the case of feedforward loops.