Light-assisted small-molecule screening against protein kinases

The combination of a light-activated receptor tyrosine kinase and a fluorescent MAPK/ERK reporter results in the development of an optogenetics-based cell screening method to identify small-molecule inhibitors of RTK signaling. High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.