ArticleScience (New York, N.Y.)2019
A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers.
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Who cites it
211 citing papers in PubMed, 371 citations in OpenAlex.
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cis glycan-glycan interactions organize membrane nanodomains that tune receptor signaling.Nature communications · 2026Article
- Proteomic investigation of signaling dynamics: from static maps to network rewiring.Bioscience reports · 2026Review
- Article
- Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Active RNA synthesis patterns nuclear condensates.Cell systems · 2026Article
- Mesoscale simulations of membrane-tethered reactions to parameterize cell-scale models of signaling.Biophysical journal · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- The double histone fold: Structure, functional implications across the tree of life and relevance to protein design.Protein science : a publication of the Protein Society · 2026Review
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- PD1-induced Shp2 condensation organizes inhibitory signalosomes through selective substrate partitioning.bioRxiv : the preprint server for biology · 2026Article
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Density transitions in the regulation of transcription.Molecular cell · 2026Review
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Delivery of peptide coacervates to form stable interaction hubs in cells.Nature communications · 2026Article
- Spontaneous switching in a protein signalling array reveals near-critical cooperativity.Nature physics · 2026Article
- Activation of α2-adrenergic receptors as a therapeutic strategy for immune rejection in post-surgery osteosarcoma recurrence treatment.Journal of orthopaedic translation · 2026Article
- A unifying model of LAT condensates in reconstitution experiments.bioRxiv : the preprint server for biology · 2025Article
151 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) is a key Ras activator that is autoinhibited in the cytosol and activates upon membrane recruitment. Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and activation. In this study, we designed a single-molecule assay to resolve the time between initial receptor-mediated membrane recruitment and the initiation of GEF activity of individual SOS molecules on microarrays of Ras-functionalized supported membranes. The rise-and-fall shape of the measured SOS activation time distribution and the long mean time scale to activation (~50 seconds) establish a basis for kinetic proofreading in the receptor-mediated activation of Ras. We further demonstrate that this kinetic proofreading is modulated by the LAT (linker for activation of T cells)-Grb2-SOS phosphotyrosine-driven phase transition at the membrane.
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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.