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  Transformation of receptor tyrosine kinases into glutamate receptors and photoreceptors

Leippe, P., Broichhagen, J., Cailliau, K., Mougel, A., Morel, M., Dissous, C., et al. (2019). Transformation of receptor tyrosine kinases into glutamate receptors and photoreceptors. Angewandte Chemie, e-pup(e-pup): 352, pp. 1-6. doi:10.1002/ange.201915352.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-6D5F-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-879B-4
Genre: Journal Article

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 Creators:
Leippe, Philipp1, Author              
Broichhagen, Johannes1, Author              
Cailliau, Katia, Author
Mougel, Alexandra, Author
Morel, Marion, Author
Dissous, Colette, Author
Vicogne, Jérôme, Author
Trauner , Dirk, Author
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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Free keywords: receptor tyrosine kinase; insulin receptor; met receptor; metabotropic glutamate receptor; photopharmacology
 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 achieved the transformation of 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 by covalent attachment of a synthetic, glutamate‐based photoswitch onto a self‐labelling SNAP tag. Employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed LihIR (Light‐controlled human Insulin Receptor) and LihMET (Light‐controlled human MET Receptor), can be used to exert optical control over insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors.

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Language(s): eng - English
 Dates: 2019-12-23
 Publication Status: Published in print
 Pages: 6
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1002/ange.201915352
 Degree: -

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Title: Angewandte Chemie
  Abbreviation : Angew. Chem.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: e-pup (e-pup) Sequence Number: 352 Start / End Page: 1 - 6 Identifier: ISSN: 0044-8249
CoNE: https://pure.mpg.de/cone/journals/resource/954926979058_1