title: Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells.
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.
authors.affiliation: Institute of Physical and Theoretical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Str, 7, 60438 Frankfurt, Germany. Hartmut.Niemann@uni-bielefeld.de.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Dietz
authors.forename: Daniel
authors.initials: D
authors.lastname: Haße
authors.forename: Davide M
authors.initials: DM
authors.lastname: Ferraris
authors.forename: Antonia
authors.initials: A
authors.lastname: Göhler
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Niemann
authors.forename: Mike
authors.initials: M
authors.lastname: Heilemann