Search our Database of Scientific Publications and Authors

I’m looking for a
    Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells.
    BMC Biophys 2013 Jun 3;6(1). Epub 2013 Jun 3.
    Institute of Physical and Theoretical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Str, 7, 60438 Frankfurt, Germany.
    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.

    Similar Publications

    Structural basis of MET receptor dimerization by the bacterial invasion protein InlB and the HGF/SF splice variant NK1.
    Biochim Biophys Acta 2013 Oct 31;1834(10):2195-204. Epub 2012 Oct 31.
    Department of Chemistry and Center for Biotechnology (CeBiTec), Bielefeld University, 33501 Bielefeld, Germany. Electronic address:
    The structural basis of ligand-induced dimerization of the receptor tyrosine kinase MET by its natural ligand hepatocyte growth factor/scatter factor (HGF/SF) is not well understood. However, interesting insight into the molecular mechanism of MET dimerization has emerged from crystal structures of MET in complex with a bacterial agonist, the invasion protein internalin B (InlB) from pathogenic Listeria monocytogenes. MET activation by InlB promotes uptake of bacteria into host cells. Read More
    Live cell imaging shows hepatocyte growth factor-induced Met dimerization.
    Biochim Biophys Acta 2016 Jul 17;1863(7 Pt A):1552-8. Epub 2016 Apr 17.
    Karlsruhe Institute of Technology (KIT), Institute of Toxicology and Genetics (ITG), Postfach 3640, 76021 Karlsruhe, Germany. Electronic address:
    The canonical model of receptor tyrosine kinase (RTK) activation assumes that ligand-induced dimerization of inactive receptor monomers is a prerequisite for autophosphorylation. For several RTK families, recent results of fluorescence microscopy provided evidence for preformed receptor dimers that may or may not require ligand binding for kinase activity. Here we report, for the first time, the application of advanced quantitative fluorescence microscopy techniques to study changes in the oligomerization state of the RTK Met in response to stimulation by its endogenous ligand hepatocyte growth factor (HGF). Read More
    Membrane dynamics of resting and internalin B-bound MET receptor tyrosine kinase studied by single-molecule tracking.
    FEBS Open Bio 2017 Sep 29;7(9):1422-1440. Epub 2017 Aug 29.
    Institute of Physical and Theoretical ChemistryJohann Wolfgang Goethe-UniversityFrankfurtGermany.
    The human MET receptor tyrosine kinase contributes to vertebrate development and cell proliferation. As a proto-oncogene, it is a target in cancer therapies. MET is also relevant for bacterial infection by Listeria monocytogenes and is activated by the bacterial protein internalin B. Read More
    Met receptor tyrosine kinase degradation is altered in response to the leucine-rich repeat of the Listeria invasion protein internalin B.
    J Biol Chem 2009 Jan 6;284(2):774-83. Epub 2008 Nov 6.
    Department of Neuroscience and Cell Biology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-1074, USA.
    Entry of the bacterial pathogen Listeria monocytogenes into host epithelial cells is critical for infection and virulence. One major pathway for Listeria entry involves binding of the bacterial protein Internalin B to the host receptor tyrosine kinase Met (hepatocyte growth factor receptor). Activation of Met and downstream signaling cascades is critical for Listeria entry. Read More