Premium
Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors
Author(s) -
Leippe Philipp,
Broichhagen Johannes,
Cailliau Katia,
Mougel Alexandra,
Morel Marion,
Dissous Colette,
Trauner Dirk,
Vicogne Jérôme
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915352
Subject(s) - receptor tyrosine kinase , ror1 , microbiology and biotechnology , metabotropic glutamate receptor , biology , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 2 , biochemistry , metabotropic glutamate receptor 5 , insulin receptor , tyrosine kinase , receptor , chemistry , platelet derived growth factor receptor , glutamate receptor , insulin , endocrinology , insulin resistance , growth factor
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.