Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors. (4th March 2020)

• Record Type: Journal Article
• Authors: Leippe, Philipp; Broichhagen, Johannes; Cailliau, Katia; Mougel, Alexandra; Morel, Marion; Dissous, Colette; Trauner, Dirk; Vicogne, Jérôme
• Is Part Of: Angewandte Chemie. Volume 132:Number 17(2020)
• Page Start: 6786
• Page End: 6789
• Publication Date: 2020-03-04
• Subjects: Photopharmakologie -- Rezeptor-Tyrosinkinasen -- Signaltransduktion -- Synthetische Biologie -- Venus-Kinase-Rezeptoren; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201915352
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Durch Kombination von Protein‐Engineering und chemischer Synthese wurde der menschliche Insulinrezeptor, eine Rezeptor‐Tyrosinkinase (RTK), in einen Glutamatrezeptor (rot) und dann in einen Photorezeptor umgewandelt. Die daraus resultierende chimäre RTK (grau) kann zur optischen Kontrolle des Insulinsignalweges verwendet werden. Der gleiche Ansatz wurde auch auf den Rezeptor für den Hepatozyten‐Wachstumsfaktor angewendet.