Spatio-temporally precise activation of engineered receptor tyrosine kinases by light

M. Grusch, K. Schelch, R. Riedler, E. Gschaider-Reichhart, C. Differ, W. Berger, Á. Inglés Prieto, H.L. Janovjak, EMBO Journal 33 (2014) 1713–1726.


Journal Article | Published | English
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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.
Publishing Year
Date Published
2014-07-01
Journal Title
EMBO Journal
Acknowledgement
European Union Seventh Framework Programme; Human Frontier Science Program; Oesterreichische Nationalbank Anniversary Fund 14211; Austrian Research Promotion Agency; FemTech
Volume
33
Issue
15
Page
1713 - 1726
IST-REx-ID

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Grusch M, Schelch K, Riedler R, et al. Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. EMBO Journal. 2014;33(15):1713-1726. doi:10.15252/embj.201387695
Grusch, M., Schelch, K., Riedler, R., Gschaider-Reichhart, E., Differ, C., Berger, W., … Janovjak, H. L. (2014). Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. EMBO Journal, 33(15), 1713–1726. https://doi.org/10.15252/embj.201387695
Grusch, Michael, Karin Schelch, Robert Riedler, Eva Gschaider-Reichhart, Christopher Differ, Walter Berger, Álvaro Inglés Prieto, and Harald L Janovjak. “Spatio-Temporally Precise Activation of Engineered Receptor Tyrosine Kinases by Light.” EMBO Journal 33, no. 15 (2014): 1713–26. https://doi.org/10.15252/embj.201387695.
M. Grusch et al., “Spatio-temporally precise activation of engineered receptor tyrosine kinases by light,” EMBO Journal, vol. 33, no. 15, pp. 1713–1726, 2014.
Grusch M, Schelch K, Riedler R, Gschaider-Reichhart E, Differ C, Berger W, Inglés Prieto Á, Janovjak HL. 2014. Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. EMBO Journal. 33(15), 1713–1726.
Grusch, Michael, et al. “Spatio-Temporally Precise Activation of Engineered Receptor Tyrosine Kinases by Light.” EMBO Journal, vol. 33, no. 15, Wiley-Blackwell, 2014, pp. 1713–26, doi:10.15252/embj.201387695.

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