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Kinase inhibition profiles as a tool to identify kinases for specific phosphorylation sites

Lookup NU author(s): Nikolaus Watson, Dr Tyrell Cartwright, Dr Conor LawlessORCiD, Dr Onur Sen, Professor Jonathan HigginsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


There are thousands of known cellular phosphorylation sites, but the paucity of ways to identify kinases for particular phosphorylation events remains a major roadblock for understanding kinase signaling. To address this, we here develop a generally applicable method that exploits the large number of kinase inhibitors that have been profiled on near-kinome-wide panels of protein kinases. The inhibition profile for each kinase provides a fingerprint that allows identification of unknown kinases acting on target phosphosites in cell extracts. We validate the method on diverse known kinase-phosphosite pairs, including histone kinases, EGFR autophosphorylation, and Integrin β1 phosphorylation by Src-family kinases. We also use our approach to identify the previously unknown kinases responsible for phosphorylation of INCENP at a site within a commonly phosphorylated motif in mitosis (a non-canonical target of Cyclin B-Cdk1), and of BCL9L at S915 (PKA). We show that the method has clear advantages over in silico and genetic screening.

Publication metadata

Author(s): Watson NA, Cartwright TN, Lawless C, Cámara-Donoso M, Sen O, Sako K, Hirota T, Kimura H, Higgins JMG

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2020

Volume: 11

Online publication date: 03/04/2020

Acceptance date: 06/03/2020

Date deposited: 20/04/2020

ISSN (electronic): 2041-1723

Publisher: Nature


DOI: 10.1038/s41467-020-15428-0


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