Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors

Philipp Leippe, Johannes Broichhagen, Katia Cailliau, Alexandra Mougel, Marion Morel, Colette Dissous, Dirk Trauner, Jérôme Vicogne

Research output: Contribution to journalArticle

Abstract

Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus kinase receptors (VKRs), an atypical family of RTKs found in nature, we have transformed the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand-binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity through covalent attachment of a synthetic glutamate-based photoswitch via a self-labelling SNAP tag. By employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed light-controlled human insulin receptor (LihIR) and light-controlled human MET receptor (LihMET), can be used to exert optical control over the insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors.

Original languageEnglish (US)
Pages (from-to)6720-6723
Number of pages4
JournalAngewandte Chemie - International Edition
Volume59
Issue number17
DOIs
StatePublished - Apr 20 2020

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Keywords

  • Venus kinase receptors
  • photopharmacology
  • receptor tyrosine kinases
  • signal transduction
  • synthetic biology

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Leippe, P., Broichhagen, J., Cailliau, K., Mougel, A., Morel, M., Dissous, C., Trauner, D., & Vicogne, J. (2020). Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors. Angewandte Chemie - International Edition, 59(17), 6720-6723. https://doi.org/10.1002/anie.201915352