Multiple Decisive Phosphorylation Sites for the Negative Feedback Regulation of SOS1 via ERK
Multiple Decisive Phosphorylation Sites for the Negative Feedback Regulation of SOS1 via ERK
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DOI：
10.1074/jbc.m110.135517
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发表时间：
2010-10-22
影响因子：
4.8
通讯作者：
Matsuda, Michiyuki
中科院分区：
文献类型：
--
作者：
Kamioka, Yuji;Yasuda, Shuhei;Matsuda, Michiyuki
EGF诱导的ERK激活已经通过实验和理论方法被广泛研究。在这里，我们使用了一个模拟模型，主要是基于实验确定的参数，研究ERK介导的负反馈调节的Rasguanine核苷酸交换因子，儿子的sevenless（SOS）。由于SOS1是在多个丝氨酸残基的磷酸化刺激后，我们评估的多重性的作用，通过建立两个模拟模型，我们称之为决定性和合作的磷酸化模型。这两个模型受到Ras激活持续时间和SOS 1基础磷酸化水平的限制。可能的解决方案，发现只有在决定性的模型，其中至少有三个，可能超过四个，磷酸化位点决定性地抑制SOS活性。因此，实验方法和模型分析的结合表明了SOS 1的多重磷酸化在负调控中的意想不到的作用。
EGF-induced activation of ERK has been extensively studied by both experimental and theoretical approaches. Here, we used a simulation model based mostly on experimentally determined parameters to study the ERK-mediated negative feedback regulation of the Rasguanine nucleotide exchange factor, son of sevenless (SOS). Because SOS1 is phosphorylated at multiple serine residues upon stimulation, we evaluated the role of the multiplicity by building two simulation models, which we termed the decisive and cooperative phosphorylation models. The two models were constrained by the duration of Ras activation and basal phosphorylation level of SOS1. Possible solutions were found only in the decisive model wherein at least three, and probably more than four, phosphorylation sites decisively suppress the SOS activity. Thus, the combination of experimental approaches and the model analysis has suggested an unexpected role of multiple phosphorylations of SOS1 in the negative regulation.