TY - JOUR
T1 - Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors
AU - Leippe, Philipp
AU - Broichhagen, Johannes
AU - Cailliau, Katia
AU - Mougel, Alexandra
AU - Morel, Marion
AU - Dissous, Colette
AU - Trauner, Dirk
AU - Vicogne, Jérôme
N1 - Funding Information:
P.L. and D.T. acknowledge support from the SFB 749 and FOR 1249. P.L. is grateful to the Boehringer Ingelheim Fonds for a travel grant and Prof. Dr. Kai Johnsson for support and advice. J.B. is grateful to a Studienstiftung des deutschen Volkes PhD Fellowship and an EMBO Short Term Fellowship (490–2011). P.L., J.B. and D.T. were supported by the Center for Integrated Protein Science Munich (CIPSM). D.T. acknowledges funding from the European Research Council (Advanced Grant 268795). A.M, C.D. and J.V. were supported by CNRS, INSERM and Université de Lille Nord de France. We thank Prof. Dr. Harald Janovjak (Monash), Prof. Dr. Axel Ullrich and Dr. Robert Torka (MPI Biochemistry Munich) for discussions, advice and support.
Funding Information:
P.L. and D.T. acknowledge support from the SFB 749 and FOR 1249. P.L. is grateful to the Boehringer Ingelheim Fonds for a travel grant and Prof. Dr. Kai Johnsson for support and advice. J.B. is grateful to a Studienstiftung des deutschen Volkes PhD Fellowship and an EMBO Short Term Fellowship (490–2011). P.L., J.B. and D.T. were supported by the Center for Integrated Protein Science Munich (CIPSM). D.T. acknowledges funding from the European Research Council (Advanced Grant 268795). A.M, C.D. and J.V. were supported by CNRS, INSERM and Université de Lille Nord de France. We thank Prof. Dr. Harald Janovjak (Monash), Prof. Dr. Axel Ullrich and Dr. Robert Torka (MPI Biochemistry Munich) for discussions, advice and support.
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/4/20
Y1 - 2020/4/20
N2 - 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.
AB - 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.
KW - Venus kinase receptors
KW - photopharmacology
KW - receptor tyrosine kinases
KW - signal transduction
KW - synthetic biology
UR - http://www.scopus.com/inward/record.url?scp=85082331035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082331035&partnerID=8YFLogxK
U2 - 10.1002/anie.201915352
DO - 10.1002/anie.201915352
M3 - Article
C2 - 31872568
AN - SCOPUS:85082331035
SN - 1433-7851
VL - 59
SP - 6720
EP - 6723
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 17
ER -