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Nuclear Functions of the Tyrosine Kinase Src
Open AccessArticle

Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation

1
Single Molecule Biophysics, Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 7, 60438 Frankfurt, Germany
2
SomaLogic, Inc., Boulder, CO 80301, USA
3
Department of Physics and Center for Nanoscience, Ludwig Maximilian University, 80539 Munich, Germany
4
Max Planck Institute of Biochemistry, 82152 Planegg, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2803; https://doi.org/10.3390/ijms21082803
Received: 20 January 2020 / Revised: 6 April 2020 / Accepted: 15 April 2020 / Published: 17 April 2020
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors. View Full-Text
Keywords: receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT
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MDPI and ACS Style

Harwardt, M.-L.I.; Schröder, M.S.; Li, Y.; Malkusch, S.; Freund, P.; Gupta, S.; Janjic, N.; Strauss, S.; Jungmann, R.; Dietz, M.S.; Heilemann, M. Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation. Int. J. Mol. Sci. 2020, 21, 2803.

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