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Receptor tyrosine kinases (RTKs) are a family of surface receptors that control diverse cellular functions, including cell proliferation, migration and differentiation. By combining RTKs with the PHR domain, a light-responsive, homo-interacting module of cryptochrome 2 protein from Arabidopsis thaliana, it is possible to create multiple synthetic RTKs that can be regulated by light with high spatiotemporal resolution. The main aim of this chapter is to serve as a guide for producing new optogenetic tools, and to this end we provide an experimental overview of the generation of optogenetic RTKs (optoRTKs) using the PHR domain as an actuator, the signaling activation characteristics of optoRTKs under different activation conditions and methods to enhance the performance of optoRTKs using improved actuators.

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