Substrate-dependent control of MAPK phosphorylation in vivo
Substrate-dependent control of MAPK phosphorylation in vivo
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DOI：
10.1038/msb.2010.121
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发表时间：
2011-02-01
影响因子：
9.9
通讯作者：
Shvartsman, Stanislav Y.
中科院分区：
文献类型：
--
作者：
Kim, Yoosik;Paroush, Ze'ev;Shvartsman, Stanislav Y.
丝裂原活化蛋白激酶(MAPK)的磷酸化对于其酶活性和控制细胞内多种底物的能力是必不可少的。根据目前的模型，MAPK磷酸化的控制与其底物无关，底物被视为MAPK活性的单纯传感器。与MAPK信号的这种模块化观点相反，我们在果蝇胚胎中的研究表明，底物可以调节体内MAPK的磷酸化水平。我们证明，单一底物的基因剂量的双重变化可以引起MAPK的磷酸化水平和其他底物的转化的显着变化。我们的结果支持一个模型，即MAPK的底物抵消了它被磷酸酶去磷酸化的作用。底物依赖的MAPK磷酸化控制是一种更普遍的追溯效应的表现，这应该是所有具有共价修饰循环的网络所固有的。《分子系统生物学》7：467；2011年2月1日在线出版；doi：10.1038/msb.2010.121
Phosphorylation of the mitogen-activated protein kinase (MAPK) is essential for its enzymatic activity and ability to control multiple substrates inside a cell. According to the current models, control of MAPK phosphorylation is independent of its substrates, which are viewed as mere sensors of MAPK activity. Contrary to this modular view of MAPK signaling, our studies in the Drosophila embryo demonstrate that substrates can regulate the level of MAPK phosphorylation in vivo. We demonstrate that a twofold change in the gene dosage of a single substrate can induce a significant change in the phosphorylation level of MAPK and in the conversion of other substrates. Our results support a model where substrates of MAPK counteract its dephosphorylation by phosphatases. Substrate-dependent control of MAPK phosphorylation is a manifestation of a more general retroactive effect that should be intrinsic to all networks with covalent modification cycles. Molecular Systems Biology 7: 467; published online 1 February 2011; doi: 10.1038/msb.2010.121