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

Michael Grusch, Karin Schelch, Robert Riedler, Eva Reichhart, Christopher Differ, Walter Berger, Álvaro Inglés-Prieto, Harald Janovjak

Research output: Contribution to journalArticleResearchpeer-review

123 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1713-1726
Number of pages14
JournalThe EMBO Journal
Volume33
Issue number15
DOIs
Publication statusPublished - 1 Aug 2014
Externally publishedYes

Keywords

  • aureochrome
  • cell signalling
  • light-oxygen-voltage (LOV)-sensing domain
  • optogenetics
  • synthetic biology
  • synthetic physiology

Cite this

Grusch, M., Schelch, K., Riedler, R., Reichhart, E., Differ, C., Berger, W., Inglés-Prieto, Á., & Janovjak, H. (2014). Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. The EMBO Journal, 33(15), 1713-1726. https://doi.org/10.15252/embj.201387695