{
  "abstract": "Upon ligand binding, the kinase domain of EGFR phosphorylates multiple tyrosine residues on the receptor cytoplasmic tail through a trans-autophosphorylation process. Phosphotyrosine sites on activated receptors recruit Grb2, which further recruits SOS to initiate downstream signaling by activating Ras. Multivalent binding between SOS and Grb2, as well as direct Grb2:Grb2 interactions, contribute to formation of a protein condensate of activated EGFR. The condensed state of EGFR facilitates autoinhibition release in SOS and exerts regulatory control over signal propagation from activated EGFR to Ras. While kinase activity of EGFR is an essential driver of this signaling process, phosphorylation at residue Y160 on Grb2 blocks Grb2:Grb2 binding and can interfere with EGFR condensation. Here, using a reconstituted system, we examine how titrating kinase activity in the EGFR system can both promote and inhibit signal output to Ras. The results reveal how effects of tyrosine kinase inhibition can, under some circumstances, promote Ras activation by inhibiting negative feedback through Grb2 phosphorylation and disruption of a Grb2 SH2/SH3 dimer interface.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of California Berkeley, Berkeley, California, United States of America.",
    "Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.",
    "California Institute for Quantitative Biosciences, University of California, Berkeley, California, United States of America.",
    "Divisions of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Henry T Phan",
      "orcid": "0000-0001-7140-0480"
    },
    {
      "affs": [
        1
      ],
      "name": "Chun-Wei Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Brittany L Stinger"
    },
    {
      "affs": [
        0
      ],
      "name": "Joseph B DeGrandchamp"
    },
    {
      "affs": [
        0
      ],
      "name": "L J Nugent Lew"
    },
    {
      "affs": [
        0
      ],
      "name": "Serena J Huang"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Jay T Groves",
      "orcid": "0000-0002-3037-5220"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bwafkkw4c33m2.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0361303",
  "fulltext_url": "https://europepmc.org/articles/PMC13704879",
  "id": "bwafkkw4c33m2",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0361303",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Kinase Regulation and GTPase Signaling"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzyme inhibitors/Kinase inhibitors"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Protein kinases/Tyrosine kinases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Lipids"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes/Protein kinases/Tyrosine kinases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Post-translational modification/Phosphorylation"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/EGFR signaling"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Ras signaling"
    ],
    [
      "plos",
      "/Physical sciences/Chemistry/Polymer chemistry/Dimers"
    ],
    [
      "plos",
      "/Physical sciences/Materials science/Materials/Oligomers/Dimers"
    ],
    [
      "plos",
      "/Physical sciences/Physics/Condensed matter physics/Phase transitions/Condensation"
    ]
  ],
  "openalex": "W7223687433",
  "pdf_url": "https://europepmc.org/articles/PMC13704879?pdf=render",
  "pmcid": "PMC13704879",
  "pmid": "42932368",
  "published": "2026-10-26",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/bwafkkw4c33m2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
      "native_id": "10.1371/journal.pone.0361303",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0361303"
    },
    {
      "first_seen": "2026-10-30T12:21:51Z",
      "native_id": "MED:42932368",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42932368"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:enzymology",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "chemistry",
      "origin": "plos:polymer chemistry",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Grb2 phosphorylation antagonizes EGFR-driven ras activation by interfering with condensate assembly",
  "title_text": "Grb2 phosphorylation antagonizes EGFR-driven ras activation by interfering with condensate assembly",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:51Z",
  "url": "https://research.draconitic.com/paper/bwafkkw4c33m2",
  "venue": "PLOS One",
  "versions": []
}