TY  - JOUR
AU  - Sun, De-En
AU  - Ng, Siu Wang
AU  - Zheng, Yu
AU  - Xie, Shu
AU  - Schwan, Niklas
AU  - Breuer, Paula
AU  - Hoffmann, Dirk Carsten Frieder
AU  - Michel, Julius Jakob
AU  - Azorin, Daniel D
AU  - Boonekamp, Kim Elisabeth
AU  - Winkler, Frank
AU  - Wick, Wolfgang
AU  - Boutros, Michael
AU  - Li, Yulong
AU  - Johnsson, Kai
TI  - Molecular recording of cellular protein kinase activity with chemical labeling.
JO  - Nature chemical biology
VL  - nn
SN  - 1552-4450
CY  - Basingstoke
PB  - Nature Publishing Group
M1  - DKFZ-2025-01370
SP  - nn
PY  - 2025
N1  - epub
AB  - Protein kinases control most cellular processes and aberrant kinase activity is involved in numerous diseases. Here we introduce molecular recorders of kinase activities for later analysis to investigate the link between specific kinase activities and cellular phenotypes in heterogeneous cell populations and in vivo. Based on split-HaloTag and a phosphorylation-dependent molecular switch, our recorders become rapidly labeled in the presence of a specific kinase activity and a fluorescent HaloTag substrate. The kinase activity in a given cell controls the degree of fluorescent labeling, whereas the recording window is set by the presence of the fluorescent substrate. We designed specific recorders for four protein kinases, including protein kinase A. We apply our protein kinase A recorder to sort heterogeneous cell populations for subsequent transcriptome analysis, in genome-wide CRISPR screens to discover regulators of PKA activity and to track neuromodulation in freely moving mice.
LB  - PUB:(DE-HGF)16
C6  - pmid:40640555
DO  - DOI:10.1038/s41589-025-01949-6
UR  - https://inrepo02.dkfz.de/record/302830
ER  -