ArticleProceedings of the National Academy of Sciences of the United States of America2012
Fast rebinding increases dwell time of Src homology 2 (SH2)-containing proteins near the plasma membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Binding memory of liquid molecules.Nature communications · 2025Article
- Enzymatic Reactions Dictated by the 2D Membrane Environment.The journal of physical chemistry letters · 2025Article
- Eph receptor signaling complexes in the plasma membrane.Trends in biochemical sciences · 2024Review
- Effect of Antigen Valency on Autoreactive B-Cell Targeting.Molecular pharmaceutics · 2024Article
- Article
- Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP.Structure (London, England : 1993) · 2022Article
- Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Biomolecular condensates in membrane receptor signaling.Current opinion in cell biology · 2021Review
- Nanopore-mediated protein delivery enabling three-color single-molecule tracking in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Immunopharmacology and Quantitative Analysis of Tyrosine Kinase Signaling.Current protocols in immunology · 2020Article
- The GTPase-activating protein p120RasGAP has an evolutionarily conserved "FLVR-unique" SH2 domain.The Journal of biological chemistry · 2020Article
- Binding Revisited-Avidity in Cellular Function and Signaling.Frontiers in molecular biosciences · 2020Review
- Specificity and regulation of phosphotyrosine signaling through SH2 domains.Journal of structural biology: X · 2020Article
- Regulation of Transmembrane Signaling by Phase Separation.Annual review of biophysics · 2019Review
- Stoichiometry controls activity of phase-separated clusters of actin signaling proteins.Science (New York, N.Y.) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Receptor tyrosine kinases (RTKs) control a host of biological functions by phosphorylating tyrosine residues of intracellular proteins upon extracellular ligand binding. The phosphotyrosines (p-Tyr) then recruit a subset of ∼100 Src homology 2 (SH2) domain-containing proteins to the cell membrane. The in vivo kinetics of this process are not well understood. Here we use total internal reflection (TIR) microscopy and single-molecule imaging to monitor interactions between SH2 modules and p-Tyr sites near the cell membrane. We found that the dwell time of SH2 modules within the TIR illumination field is significantly longer than predictions based on chemical dissociation rate constants, suggesting that SH2 modules quickly rebind to nearby p-Tyr sites after dissociation. We also found that, consistent with the rebinding model, the effective diffusion constant is negatively correlated with the respective dwell time for different SH2 domains and the dwell time is positively correlated with the local density of RTK phosphorylation. These results suggest a mechanism whereby signal output can be regulated through the spatial organization of multiple binding sites, which will prompt reevaluation of many aspects of RTK signaling, such as signaling specificity, mechanisms of spatial control, and noise suppression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.