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Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

BACKGROUND: The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious disease...

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Autores principales: Dietz, Marina S, Haße, Daniel, Ferraris, Davide M, Göhler, Antonia, Niemann, Hartmut H, Heilemann, Mike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674922/
https://www.ncbi.nlm.nih.gov/pubmed/23731667
http://dx.doi.org/10.1186/2046-1682-6-6
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author Dietz, Marina S
Haße, Daniel
Ferraris, Davide M
Göhler, Antonia
Niemann, Hartmut H
Heilemann, Mike
author_facet Dietz, Marina S
Haße, Daniel
Ferraris, Davide M
Göhler, Antonia
Niemann, Hartmut H
Heilemann, Mike
author_sort Dietz, Marina S
collection PubMed
description BACKGROUND: The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. RESULTS: To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. CONCLUSIONS: Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.
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spelling pubmed-36749222013-06-10 Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells Dietz, Marina S Haße, Daniel Ferraris, Davide M Göhler, Antonia Niemann, Hartmut H Heilemann, Mike BMC Biophys Research Article BACKGROUND: The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. RESULTS: To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. CONCLUSIONS: Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases. BioMed Central 2013-06-03 /pmc/articles/PMC3674922/ /pubmed/23731667 http://dx.doi.org/10.1186/2046-1682-6-6 Text en Copyright © 2013 Dietz et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dietz, Marina S
Haße, Daniel
Ferraris, Davide M
Göhler, Antonia
Niemann, Hartmut H
Heilemann, Mike
Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title_full Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title_fullStr Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title_full_unstemmed Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title_short Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells
title_sort single-molecule photobleaching reveals increased met receptor dimerization upon ligand binding in intact cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674922/
https://www.ncbi.nlm.nih.gov/pubmed/23731667
http://dx.doi.org/10.1186/2046-1682-6-6
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