Yang Liu, Zhu Audrey, Aman Javed M, Denberg David, Kilwein Marcus D, Marmion Robert A, Johnson Alex N T, Veraksa Alexey, Singh Mona, Wühr Martin, Shvartsman Stanislav Y
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Dev Cell. 2024 Dec 2;59(23):3061-3071.e6. doi: 10.1016/j.devcel.2024.08.004. Epub 2024 Aug 28.
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.
细胞外信号调节激酶（ERK）信号传导控制着发育和体内平衡，并且在包括神经认知障碍和癌症在内的人类疾病中发生基因失调。尽管ERK的功能众多且不断增加，但任何特定ERK激活事件所控制的全部过程仍不为人知。在这里，我们展示了如何使用靶向扰动和ERK激活的全局读数来系统地识别ERK的功能。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相结合，我们证明了两极的ERK激活对于维持胚胎分裂的速度和同步性也至关重要。所提出的研究磷酸化网络的方法确定了一个经过充分研究的信号事件的隐藏功能，并为其他生物体的类似研究奠定了基础。
