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Abstract：
Ras is a small GTPase that is central to important functional decisions in diverse cell types. An important aspect of Ras signaling is its ability to exhibit bimodal or switch-like activity. We describe the total reconstitution of a receptor-mediated Ras activation-deactivation reaction catalyzed by SOS and p120-RasGAP on supported lipid membrane microarrays. The results reveal a bimodal Ras activation response, which is not a result of deterministic bistability but is rather driven by the distinct processivity of the Ras activator, SOS. Furthermore, the bimodal response is controlled by the condensation state of the scaffold protein, LAT, to which SOS is recruited. Processivity-driven bimodality leads to stochastic bursts of Ras activation even under strongly deactivating conditions. This behavior contrasts deterministic bistability and may be more resistant to pharmacological inhibition.
摘要：
Ras是一种小的GTP酶，对不同细胞类型的重要功能决定至关重要。Ras信号传导的一个重要方面是其表现出双峰或开关样活性的能力。我们描述了在支持的脂质膜微阵列上由SOS和p120-RasGAP催化的受体介导的Ras激活-失活反应的完全重建。结果显示了双峰Ras激活反应，这不是确定性双稳态的结果，而是由Ras活化剂的独特的可加工性驱动的，求救信号.此外，双峰反应由支架蛋白的缩合状态控制，LAT,SOS被招募的人。即使在强烈的去激活条件下，过程性驱动的双峰性也会导致Ras激活的随机爆发。这种行为与确定性双稳态相反，并且可能对药理学抑制更具抵抗力。
