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Spatio‐temporally precise activation of engineered receptor tyrosine kinases by light
Author(s) -
Grusch Michael,
Schelch Karin,
Riedler Robert,
Reichhart Eva,
Differ Christopher,
Berger Walter,
InglésPrieto Álvaro,
Janovjak Harald
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201387695
Subject(s) - biology , microbiology and biotechnology , receptor tyrosine kinase , optogenetics , fibroblast growth factor , fibroblast growth factor receptor , receptor , kinase , tyrosine kinase , epidermal growth factor receptor , signal transduction , biochemistry , neuroscience
Receptor tyrosine kinases ( RTK s) 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 RTK s with spatial and temporal precision is currently not feasible. Here, we generated RTK s 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 RTK s 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 ( FGFR 1), 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. RTK s under optical control ( O pto‐ RTK s) provide a powerful optogenetic approach to actuate cellular signals and manipulate cell behaviour.