Phosphatases regulating ERK activation and ERK-dependent cell migration.

EYA family phosphatases are critical regulators of ERK signaling in both Drosophila and mammalian cells, and inhibiting human EYA4 enhances migration of ERK-responsive tumor cells.

• Why it matters: ERK activity is controlled by phosphorylation and dephosphorylation, but the specific phosphatases that regulate ERK signaling dynamics and downstream migration are not fully defined.
• What they did: The team adapted a live-cell method to monitor ERK activity and screened 140 human phosphatases using the ERK-SPARK reporter, then validated phosphatase homologs in an in vivo Drosophila model.
• The result: EYA family phosphatases emerged as key ERK regulators across species, and blocking human EYA4 increased migration of ERK-responsive tumor cells, informing therapeutic targeting strategies.

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