激酶和磷酸酶之间的协调对于调节必需信号分子的磷酸化水平至关重要。能够精确控制激酶活性的方法对于了解激酶功能和开发靶向治疗非常有价值。在这里，我们使用脱落酸（ABA）诱导的邻近系统通过招募磷酸酶来可逆地控制激酶信号传导。使用这种方法，我们发现致癌酪氨酸激酶 BCR::ABL1 可以通过招募各种细胞质磷酸酶来抑制。我们还发现，据报道，致癌丝氨酸/苏氨酸激酶 BRAF(V600E) 可以绕过磷酸化调节，可以受到蛋白磷酸酶 1 (PP1) 的正向调节，并受到 PP5 的负向调节。此外，我们观察到双特异性激酶 MEK1 可以通过招募 PP5 来抑制。这表明能够将 PP5 招募到 MEK 或 RAF 激酶的双功能分子可能是有前途的抗癌药物候选者。因此，ABA 诱导的去磷酸化方法能够快速筛选磷酸酶以精确控制激酶信号传导。© 2024。作者。

The coordination between kinases and phosphatases is crucial for regulating the phosphorylation levels of essential signaling molecules. Methods enabling precise control of kinase activities are valuable for understanding the kinase functions and for developing targeted therapies. Here, we use the abscisic acid (ABA)-induced proximity system to reversibly control kinase signaling by recruiting phosphatases. Using this method, we found that the oncogenic tyrosine kinase BCR::ABL1 can be inhibited by recruiting various cytoplasmic phosphatases. We also discovered that the oncogenic serine/threonine kinase BRAF(V600E), which has been reported to bypass phosphorylation regulation, can be positively regulated by protein phosphatase 1 (PP1) and negatively regulated by PP5. Additionally, we observed that the dual-specificity kinase MEK1 can be inhibited by recruiting PP5. This suggests that bifunctional molecules capable of recruiting PP5 to MEK or RAF kinases could be promising anticancer drug candidates. Thus, the ABA-induced dephosphorylation method enables rapid screening of phosphatases to precisely control kinase signaling.© 2024. The Author(s).