ArticleProceedings of the National Academy of Sciences of the United States of America2007
Multiple-state reactions between the epidermal growth factor receptor and Grb2 as observed by using single-molecule analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 91 citations in OpenAlex.
- Quantitative Mapping of Nanoscale EGFR-Grb2 Assemblies by DNA-PAINT.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Systems-level consequences of low RAF abundance for EGFR-ERK signaling.Biophysical journal · 2026Article
- Single-Molecule FRET-Tracking of InlB-Activated MET Receptors in Living Cells.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Cell cycle dependence of ERK activation dynamics is regulated by PI3K and PAK1 signaling.Scientific reports · 2025Article
- Enzymatic Reactions Dictated by the 2D Membrane Environment.The journal of physical chemistry letters · 2025Article
- Laminar organization of molecular complexes in a clathrin coat revealed by nanoscale protein colocalization.Structure (London, England : 1993) · 2025Article
- Spatial and signaling overlap of growth factor receptor systems at clathrin-coated sites.Molecular biology of the cell · 2024Article
- Crosstalk of growth factor receptors at plasma membrane clathrin-coated sites.bioRxiv : the preprint server for biology · 2024Article
- Electric field modulation of ERK dynamics shows dependency on waveform and timing.Scientific reports · 2024Article
- Breakdown of Langmuir Adsorption Isotherm in Small Closed Systems.Langmuir : the ACS journal of surfaces and colloids · 2024Article
- Application of single-molecule analysis to singularity phenomenon of cells.Biophysics and physicobiology · 2024Article
- Ultrafast single-molecule imaging reveals focal adhesion nano-architecture and molecular dynamics.The Journal of cell biology · 2023Article
- Multimerizations, Aggregation, and Transfer Reactions of Small Numbers of Molecules.Journal of chemical information and modeling · 2023Article
- Article
- p52Shc regulates the sustainability of ERK activation in a RAF-independent manner.Molecular biology of the cell · 2021Article
- In-Cell Single-Molecule Analysis of Molecular State and Reaction Kinetics Coupling.Advances in experimental medicine and biology · 2021Article
- Biphasic spatiotemporal regulation of GRB2 dynamics by p52SHC for transient RAS activation.Biophysics and physicobiology · 2021Article
- Extracting Transition Rates in Particle Tracking Using Analytical Diffusion Distribution Analysis.Biophysical journal · 2020Article
- Specificity and regulation of phosphotyrosine signaling through SH2 domains.Journal of structural biology: X · 2020Article
- Minute-scale persistence of a GPCR conformation state triggered by non-cognate G protein interactions primes signaling.Nature communications · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation of the cytoplasmic tyrosine residues of the epidermal growth factor receptor (EGFR) upon binding of EGF induces recognition of various intracellular signaling molecules, including Grb2. Here, the reaction kinetics between EGFR and Grb2 was analyzed by visualizing single molecules of Grb2 conjugated to the fluorophore Cy3 (Cy3-Grb2). The plasma membrane fraction was purified from human epithelial carcinoma A431 cells after stimulation with EGF and attached to coverslips. Unitary events of association and dissociation of Cy3-Grb2 on the EGFR in the membrane fraction were observed at different concentrations of Grb2 (0.1-100 nM). The dissociation kinetics could be explained by using a multiple-exponential function with a major (>90%) dissociation rate of 8 s(-1) and a few minor components, suggesting the presence of multiple bound states. In contrast, the association kinetics could be described by a stretched exponential function, suggesting the presence of multiple reaction channels from many unbound substates. Transitions between the unbound substates were also suggested. Unexpectedly, the rate of association was not proportional to the Grb2 concentration: an increase in Cy3-Grb2 concentration by a factor of 10 induced an increase in the reaction frequency approximately by a factor of three. This effect can compensate for fluctuation of the signal transduction from EGFR to Grb2 caused by variations in the expression level of Grb2 in living cells.
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