细胞外信号调节激酶 (ERK) 信号控制发育和稳态，并且在人类疾病（包括神经认知障碍和癌症）中受到基因失调的影响。尽管 ERK 功能列表庞大且稳定增长，但由任何特定 ERK 激活事件控制的全部过程仍然未知。在这里，我们展示了如何使用有针对性的扰动和 ERK 激活的全局读数来系统地识别 ERK 功能。我们的实验模型是果蝇胚胎，迄今为止，胚胎两极的 ERK 信号传导仅与未来幼虫的转录模式相关。通过实时成像和磷酸化蛋白质组学的结合，我们证明了两极的 ERK 激活对于维持胚胎卵裂的速度和同步性也至关重要。所提出的询问磷酸化网络的方法确定了经过充分研究的信号事件的隐藏功能，并为其他生物体中的类似研究奠定了基础。版权所有 © 2024。由爱思唯尔公司出版。

Extracellular-signal-regulated kinase (ERK) signaling controls development and homeostasis and is genetically deregulated in human diseases, including neurocognitive disorders and cancers. Although the list of ERK functions is vast and steadily growing, the full spectrum of processes controlled by any specific ERK activation event remains unknown. Here, we show how ERK functions can be systematically identified using targeted perturbations and global readouts of ERK activation. Our experimental model is the Drosophila embryo, where ERK signaling at the embryonic poles has thus far only been associated with the transcriptional patterning of the future larva. Through a combination of live imaging and phosphoproteomics, we demonstrated that ERK activation at the poles is also critical for maintaining the speed and synchrony of embryonic cleavages. The presented approach to interrogating phosphorylation networks identifies a hidden function of a well-studied signaling event and sets the stage for similar studies in other organisms.Copyright © 2024. Published by Elsevier Inc.