Optical control of cell signaling by single-chain photoswitchable kinases

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Science  24 Feb 2017:
Vol. 355, Issue 6327, pp. 836-842
DOI: 10.1126/science.aah3605

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Shining a light on cell signaling

Protein kinases are proteins that are used to transmit signals within cells. Zhou et al. engineered diverse kinases so that they could be switched on and off with visible light. They modified the fluorescent protein Dronpa so that instead of being tetrameric, it dimerized in violet light and dissociated in cyan light, and they fused two copies to representatives from different families of kinases. The engineered kinases could be photo-switched with spatial and temporal precision and were successfully used to study a variety of signaling pathways.

Science, this issue p. 836


Protein kinases transduce signals to regulate a wide array of cellular functions in eukaryotes. A generalizable method for optical control of kinases would enable fine spatiotemporal interrogation or manipulation of these various functions. We report the design and application of single-chain cofactor-free kinases with photoswitchable activity. We engineered a dimeric protein, pdDronpa, that dissociates in cyan light and reassociates in violet light. Attaching two pdDronpa domains at rationally selected locations in the kinase domain, we created the photoswitchable kinases psRaf1, psMEK1, psMEK2, and psCDK5. Using these photoswitchable kinases, we established an all-optical cell-based assay for screening inhibitors, uncovered a direct and rapid inhibitory feedback loop from ERK to MEK1, and mediated developmental changes and synaptic vesicle transport in vivo using light.

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