Optogenetic Tool to Control Kinase Signaling

Mitogen-Activated Protein Kinases (MAPKs) are fundamental for transmitting information through cellular signaling pathways. The activation of these kinases catalyzes the addition of phosphate groups, a mechanism known as phosphorylation, to the target molecule, and has been observed to occur in elaborate temporal patterns. Currently, there is no tool for reversibly controlling kinasesand thus mimicking those endogenous signals. In this research, we sought to create a new optogenetic tool to reversibly control a specific MAPK called ERK. We modified the wild-type ERK protein to contain a light-switchable heterodimer, which upon activation would occlude the active site of the enzyme. This allows us to turn the protein “on” or “off”using different wavelengths of light, giving us full modular control of this node of the MAPK pathway. This novel tool willallow us and others to isolate contribution of a kinase’s activityto signal transduction inthe pathway that utilizesit. We created this tooland areanalyzing the tool in a mammalian cell culture system. The next step for us will be to use this tool on other MAPKsin the same pathway as ERK and in parallel pathways. Thiswill allow usto have a better understanding of the effectsthat each kinase has on cell behaviors by isolating their activity form the enormously complexcellular signaling network.