Reversible control of kinase signaling through chemical-induced dephosphorylation.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
31 Aug 2024
31 Aug 2024
Historique:
received:
24
12
2023
accepted:
22
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
31
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39217250
doi: 10.1038/s42003-024-06771-9
pii: 10.1038/s42003-024-06771-9
doi:
Substances chimiques
Abscisic Acid
72S9A8J5GW
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
MAP Kinase Kinase 1
EC 2.7.12.2
Fusion Proteins, bcr-abl
EC 2.7.10.2
Protein Phosphatase 1
EC 3.1.3.16
BRAF protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1073Informations de copyright
© 2024. The Author(s).
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