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.

中文翻译：

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体内 MAPK 磷酸化的底物依赖性控制。

丝裂原活化蛋白激酶 (MAPK) 的磷酸化对其酶活性和控制细胞内多种底物的能力至关重要。根据目前的模型，MAPK 磷酸化的控制与其底物无关，底物仅被视为 MAPK 活性的传感器。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 磷酸化的水平。我们证明单个底物的基因剂量的双重变化可以诱导 MAPK 磷酸化水平和其他底物转化的显着变化。我们的结果支持一个模型，其中 MAPK 的底物通过磷酸酶抵消其去磷酸化。