title: Spatio-temporally precise activation of engineered receptor tyrosine kinases by light.
abstract: 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.
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Schelch
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Riedler
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Reichhart
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Differ
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Inglés-Prieto
authors.affiliation: Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria harald@ist.ac.at.
authors.forename: Harald
authors.initials: H
authors.lastname: Janovjak
mesh_terms: D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008027:Light; D010766:Phosphorylation; D015202:Protein Engineering / Q000379:methods; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011994:Recombinant Proteins; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: aureochrome; cell signalling; light‐oxygen‐voltage (LOV)‐sensing domain; optogenetics; synthetic biology; synthetic physiology