Guesdon, F., Kaabi, Y., Riley, A.H. et al. (6 more authors) (2012) Expression of a glycosylphosphatidylinositol-anchored ligand, growth hormone, blocks receptor signalling. Bioscience Reports, 32 (6). 653 - 660. ISSN 0144-8463
Abstract
We have investigated the interaction between GH (growth hormone) and GHR (GH receptor). We previously demonstrated that a truncated GHR that possesses a transmembrane domain but no cytoplasmic domain blocks receptor signalling. Based on this observation we investigated the impact of tethering the receptor's extracellular domain to the cell surface using a native lipid GPI (glycosylphosphatidylinositol) anchor. We also investigated the effect of tethering GH, the ligand itself, to the cell surface and demonstrated that tethering either the ecGHR (extracellular domain of GHR) or the ligand itself to the cell membrane via a GPI anchor greatly attenuates signalling. To elucidate the mechanism for this antagonist activity, we used confocal microscopy to examine the fluorescently modified ligand and receptor. GH–GPI was expressed on the cell surface and formed inactive receptor complexes that failed to internalize and blocked receptor activation. In conclusion, contrary to expectation, tethering an agonist to the cell surface can generate an inactive hormone receptor complex that fails to internalize.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | cytokine antagonist; growth hormone; growth hormone receptor; glycosylphosphatidylinositol anchor; signal transduction; receptor trafficking |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Sep 2015 15:53 |
Last Modified: | 23 Jun 2023 21:53 |
Published Version: | http://dx.doi.org/10.1042/BSR20120088 |
Status: | Published |
Publisher: | Portland Press |
Refereed: | Yes |
Identification Number: | 10.1042/BSR20120088 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:90203 |