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Phosphatases regulating ERK activation and ERK-dependent cell migration

Year: 2026
Type: article
Abstract: Extracellular signal-regulated kinases (ERKs) have essential roles in development and are implicated in numerous diseases. ERKs are activated by phosphorylation and are regulated by dephosphorylation. To study the ERK phosphatases, we adapted a method to monitor ERK activity in live, unfixed preparations that accommodates the highly dynamic temporal and spatial features of ERK activation. We evaluated 140 human phosphatases using an in vivo reporter (ERK-SPARK) for high-throughput screening in human cells, and we used an in vivo Drosophila model for functional validation of their phosphatase homologs. We found that EYA family phosphatases are critical regulators of ERK signaling both in Drosophila and in mammalian cells and found that inhibition of human EYA4, a homolog of Drosophila Eyes Absent phosphatase, enhances migration of ERK-responsive tumor cells. These findings have important implications for the development of therapeutics.
DOI: 10.1073/pnas.2613268123
Authors: Yue Li, Huanle Li, Tianfeng Lu, Qingcui Li, Wenrui Dou, Xiaoyi Zhu, Ming Zhong, Qiang Zhao, Junhui Guo, Thomas B. Kornberg, Honggang Wu, Xiaokun Shu, Hai Huang
Institutions: Women's Hospital, School of Medicine, Zhejiang University, Second Affiliated Hospital of Zhejiang University, Zhejiang University-University of Edinburgh Institute, Zhejiang University, University of Edinburgh, University of Chinese Academy of Sciences
Language: English
Open Access status: hybrid
OpenAlex ID: W7225793979
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Cites: 46
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