Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782272431194374144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3674922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dietzmarinas singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells AT haßedaniel singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells AT ferrarisdavidem singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells AT gohlerantonia singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells AT niemannhartmuth singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells AT heilemannmike singlemoleculephotobleachingrevealsincreasedmetreceptordimerizationuponligandbindinginintactcells |