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Open Access Highly Accessed Research article

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

Marina S Dietz1, Daniel Haße2, Davide M Ferraris3, Antonia Göhler4, Hartmut H Niemann2* and Mike Heilemann1*

Author Affiliations

1 Institute of Physical and Theoretical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Str. 7, 60438 Frankfurt, Germany

2 Structural Biochemistry, Department of Chemistry, Bielefeld University, Universitaetsstr. 25, 33615 Bielefeld, Germany

3 Department of Pharmaceutical Science, University of Eastern Piedmont “Amedeo Avogadro”, Via Bovio 6, Novara, 28100, Italy

4 Department of Biotechnology and Biophysics, Julius-Maximilians University, Am Hubland, Biozentrum, Wuerzburg, 97074, Germany

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BMC Biophysics 2013, 6:6  doi:10.1186/2046-1682-6-6

Published: 3 June 2013

Abstract

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.

Keywords:
MET receptor; Dimerization; Single-molecule photobleaching; Fluorescence correlation spectroscopy; Fluorescence; Signal transduction