{
  "abstract": "T cells can respond to even a single molecular binding event of antigen to a TCR. A key step in the TCR signaling pathway that definitively exhibits this single-molecule response is the initiation of calcium influx by activation of PLCγ1 in the LAT protein condensate. Here, we describe detailed kinetic measurements examining how protein condensation of LAT regulates activation of PLCγ1 using a reconstituted membrane system. The results reveal that membrane recruitment of PLCγ1 is tightly controlled by the LAT phosphorylation state, with no measurable independent recruitment to PIP2 or PIP3 lipids via the PLCγ1 PH domains. We further observe PLCγ1 is rapidly activated by membrane-associated kinase upon recruitment, irrespective of the LAT condensation state. These studies also reveal a crosstalk mechanism in which the TEC family kinases responsible for PLCγ1 activation also phosphorylate LAT. This interaction establishes a positive feedback loop in LAT phosphorylation, mediated through LAT condensation, which drives a bimodal LAT phosphorylation response to TCR activation. Kinetic modeling reveals how this LAT phosphorylation response can cooperatively gate PLCγ1 activation from a single TCR. These results suggest the LAT condensate facilitates both signal amplification and noise suppression in PLCγ1 activation through a bimodal switch affecting LAT phosphorylation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, University of California, Berkeley, CA 94720",
    "Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139",
    "Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37240",
    "Department of Chemistry, University of Copenhagen, Copenhagen DK-2100, Denmark"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "He Ren",
      "orcid": "0009-0007-2838-835X"
    },
    {
      "affs": [
        0
      ],
      "name": "Hyun-Ro Lee",
      "orcid": "0000-0002-1780-940X"
    },
    {
      "affs": [
        1
      ],
      "name": "Yannick A. D. Omar",
      "orcid": "0009-0000-6700-2519"
    },
    {
      "affs": [
        0
      ],
      "name": "Joseph B. DeGrandchamp",
      "orcid": "0000-0003-2194-5495"
    },
    {
      "affs": [
        2
      ],
      "name": "Chien-Lun Hung",
      "orcid": "0000-0002-2546-1132"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Timothy J. Eisen",
      "orcid": "0000-0002-4812-4171"
    },
    {
      "affs": [
        3
      ],
      "name": "Dimitrios Stamou"
    },
    {
      "affs": [
        2
      ],
      "name": "John Kuriyan",
      "orcid": "0000-0002-4414-5477"
    },
    {
      "affs": [
        1
      ],
      "name": "Arup K. Chakraborty",
      "orcid": "0000-0003-1268-9602"
    },
    {
      "affs": [
        0
      ],
      "name": "Jay T. Groves",
      "orcid": "0000-0002-3037-5220"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17yc0wn4c4j9r.bib",
  "cited_by": 1,
  "doi": "10.1073/pnas.2614738123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13643308/",
  "id": "17yc0wn4c4j9r",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2614738123",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "408"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Biophysics and Computational Biology"
    ],
    [
      "openalex",
      "1312|Protein Kinase Regulation and GTPase Signaling"
    ]
  ],
  "openalex": "W7214887377",
  "pdf_url": null,
  "pmcid": "PMC13643308",
  "pmid": "42814554",
  "published": "2026-09-30",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/17yc0wn4c4j9r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "PMC13643308",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2614738123"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Kinase Regulation and GTPase Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation",
  "title_text": "LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:29Z",
  "url": "https://research.draconitic.com/paper/17yc0wn4c4j9r",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}