Ultrasensitivity in the mitogen-activated protein kinase cascade
Ultrasensitivity in the mitogen-activated protein kinase cascade
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DOI：
10.1073/pnas.93.19.10078
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发表时间：
1996-09-17
影响因子：
11.1
通讯作者：
Ferrell, JE
中科院分区：
文献类型：
--
作者：
Huang, CYF;Ferrell, JE
有丝分裂原激活的蛋白激酶（MAPK）级联反应是一系列高度保守的三种蛋白激酶，与不同的生物学过程有关。在这里，我们证明了级联安排对MAPK信号的动态产生了意外的后果。我们从数值上解决了级联反应的速率方程，发现MAPK的行为就像是高度合作的酶，尽管没有假定级联中的任何酶受到协同调节。爪蟾卵母细胞提取物中MAPK激活的测量证实了这一预测。发现MAPK的刺激/响应曲线与山丘系数为4-5的合作酶一样陡峭，远超过经典的变构蛋白质血红蛋白。 MAPK刺激/响应曲线的形状可能使级联反应特别适合介导诸如有丝分裂发生，细胞命运诱导和卵母细胞成熟的过程，其中细胞从一个离散状态转换为另一个。
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another.