Amazing stuff!
"... researchers have developed a powerful new biosensor that reveals, in unprecedented detail, how and where kinases – enzymes that control nearly all cellular processes – turn on and off inside living cells.
The advance provides scientists with a new way to study the molecular switches that regulate cellular processes, including cell growth and DNA repair, as well as cellular responses to chemotherapy drugs and pathological conditions such as cancer.
Cells rely on kinases to control processes from cellular metabolism and growth to stress responses. Unraveling how the more than 500 kinases in human cells all work together is one of biology’s biggest puzzles. Until now, researchers lacked robust tools to see exactly where and how these enzymes act inside cells. ..."
From the abstract:
"Understanding kinase action requires precise quantitative measurements of their activity in vivo. In addition, the ability to capture spatial information of kinase activity is crucial to deconvolute complex signaling networks, interrogate multifaceted kinase actions, and assess drug effects or genetic perturbations.
Here we develop a proteomic kinase activity sensor technique (ProKAS) for the analysis of kinase signaling using mass spectrometry.
ProKAS is based on a tandem array of peptide sensors with amino acid barcodes that allow multiplexed analysis for spatial, kinetic, and screening applications.
We engineered a ProKAS module to simultaneously monitor the activities of the DNA damage response kinases ATR, ATM, and CHK1 in response to genotoxic drugs, while also uncovering differences between these signaling responses in the nucleus, cytosol, and replication factories.
Furthermore, we developed an in silico approach for the rational design of specific substrate peptides expandable to other kinases.
Overall, ProKAS is a versatile system for systematically and spatially probing kinase action in cells."
Proteomic sensors for quantitative multiplexed and spatial monitoring of kinase signaling (open access)
Fig. 1: Design and rationale of ProKAS, a modular technique for multiplexed analysis of kinase activity using mass spectrometry.
Fig. 2: Development and validation of a ProKAS sensor specific for ATR using phosphoproteomic data.
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