date: 2020-04-17T12:20:19Z
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pdf:docinfo:title: Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation
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subject: 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.
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dc:title: Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation
modified: 2020-04-17T12:20:19Z
cp:subject: 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.
pdf:docinfo:subject: 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.
pdf:docinfo:creator: Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
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meta:author: Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
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Creation-Date: 2020-04-17T12:20:19Z
Author: Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
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Keywords: receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT
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dc:creator: Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
dcterms:created: 2020-04-17T12:20:19Z
Last-Modified: 2020-04-17T12:20:19Z
dcterms:modified: 2020-04-17T12:20:19Z
title: Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation
Last-Save-Date: 2020-04-17T12:20:19Z
pdf:docinfo:keywords: receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT
pdf:docinfo:modified: 2020-04-17T12:20:19Z
meta:save-date: 2020-04-17T12:20:19Z
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creator: Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
dc:subject: receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT
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meta:keyword: receptor tyrosine kinases; MET; EGFR; receptor cross-interaction; single-molecule localization microscopy; single-particle tracking; DNA-PAINT
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pdf:docinfo:created: 2020-04-17T12:20:19Z