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Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation

ABSTRACT: Identification of covalently bound protein targets of probe WEL028 in wild-type or mutant HL-60 cells.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Tom van der Wel

LAB HEAD: Mario van der Stelt

PROVIDER: PXD018270 | Pride | 2020-05-25

REPOSITORIES: Pride

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Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis.

van der Wel Tom T Hilhorst Riet R den Dulk Hans H van den Hooven Tim T Prins Nienke M NM Wijnakker Joost A P M JAPM Florea Bogdan I BI Lenselink Eelke B EB van Westen Gerard J P GJP Ruijtenbeek Rob R Overkleeft Herman S HS Kaptein Allard A Barf Tjeerd T van der Stelt Mario M

Nature communications 20200625 1

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases. By substituting a serine residue into cysteine at the DFG-1 position in the ATP-binding pocket, we sensitize the non-receptor tyrosine kinase FES towards covalent labeling by a complementary fluorescent chemical probe. This mu ...[more]

PMID: 32587248

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Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation

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