Spatio-temporally precise activation of engineered receptor tyrosine kinases by light.
Receptor tyrosine kinases (RTKs) are a large family of cell surface receptors that sense growth factors and hormones and regulate a variety of cell behaviours in health and disease. Contactless activation of RTKs with spatial and temporal precision is currently not feasible. Here, we generated RTKs that are insensitive to endogenous ligands but can be selectively activated by low-intensity blue light. We screened light-oxygen-voltage (LOV)-sensing domains for their ability to activate RTKs by light-activated dimerization. Incorporation of LOV domains found in aureochrome photoreceptors of stramenopiles resulted in robust activation of the fibroblast growth factor receptor 1 (FGFR1), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET). In human cancer and endothelial cells, light induced cellular signalling with spatial and temporal precision. Furthermore, light faithfully mimicked complex mitogenic and morphogenic cell behaviour induced by growth factors. RTKs under optical control (Opto-RTKs) provide a powerful optogenetic approach to actuate cellular signals and manipulate cell behaviour.
['Grusch|Michael|M|', 'Schelch|Karin|K|', 'Riedler|Robert|R|', 'Reichhart|Eva|E|', 'Differ|Christopher|C|', 'Berger|Walter|W|', 'Inglés-Prieto|Álvaro|Á|', 'Janovjak|Harald|H|']
D004789:Enzyme Activation D066246:ErbB Receptors D057809:HEK293 Cells D006801:Humans D008027:Light D010766:Phosphorylation D015202:Protein Engineering D055503:Protein Multimerization D017434:Protein Structure, Tertiary D020794:Receptor Protein-Tyrosine Kinases D051496:Receptor, Fibroblast Growth Factor, Type 1 D011994:Recombinant Proteins D015398:Signal Transduction
aureochrome optogenetics cell signalling light‐oxygen‐voltage (LOV)‐sensing domain synthetic biology synthetic physiology