ArticleProceedings of the National Academy of Sciences of the United States of America2022
A two-component protein condensate of the EGFR cytoplasmic tail and Grb2 regulates Ras activation by SOS at the membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 82 citations in OpenAlex.
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- 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
- Synthetic FLS2 receptor oligomer boosts plant innate immunity.Science advances · 2026Article
- Cis glycan-glycan interactions organize membrane nanodomains that tune receptor signaling.Nature communications · 2026Article
- Article
- NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Cell-specific Cahn-Hilliard models predict condensed fates of the chromosomal passenger complex.PLoS computational biology · 2026Article
- The membrane transition strongly enhances biopolymer condensation through prewetting.Nature chemical biology · 2026Article
- Simulations show increased lipid interdigitation in transmembrane coupling of protein condensates.bioRxiv : the preprint server for biology · 2026Article
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Kinase condensates enrich ATP and trigger autophosphorylation.Cell reports · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Structural and mechanistic insights into the constitutive Themis-Grb2 complex in T cell signalling.Nature communications · 2026Article
- Quantitative Mapping of Nanoscale EGFR-Grb2 Assemblies by DNA-PAINT.Chemphyschem : a European journal of chemical physics and physical chemistry · 2026Article
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- pH-Dependent Conformational Changes in Grb2 Monomer Reveal Different Binding Sites for Coumarin: An Insight for Small Molecule Drug Discovery.ACS omega · 2026Article
- Biochemical Reconstitution and FRAP Analysis of Membrane-Associated Condensates on Supported Lipid Bilayers.Bio-protocol · 2026Article
- A phase separation hypothesis for the biological function of PrP: the role of multivalent interactions at the plasma membrane.Biochemical Society transactions · 2026Review
- Molecular basis and cellular effects of Janus-class-driven cytoplasmic PYK2 coacervates.Communications biology · 2026Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
We reconstitute a phosphotyrosine-mediated protein condensation phase transition of the ∼200 residue cytoplasmic tail of the epidermal growth factor receptor (EGFR) and the adaptor protein, Grb2, on a membrane surface. The phase transition depends on phosphorylation of the EGFR tail, which recruits Grb2, and crosslinking through a Grb2-Grb2 binding interface. The Grb2 Y160 residue plays a structurally critical role in the Grb2-Grb2 interaction, and phosphorylation or mutation of Y160 prevents EGFR:Grb2 condensation. By extending the reconstitution experiment to include the guanine nucleotide exchange factor, SOS, and its substrate Ras, we further find that the condensation state of the EGFR tail controls the ability of SOS, recruited via Grb2, to activate Ras. These results identify an EGFR:Grb2 protein condensation phase transition as a regulator of signal propagation from EGFR to the MAPK pathway.
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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.