{
  "abstract": ") is a ubiquitously expressed molecular scaffold that is known to be required for behavioral responses to certain antidepressants, presumably through its effect on G protein-coupled receptor (GPCR)-mediated signaling. Here, we demonstrate that p11 recruitment to GPCRs is promoted by an active receptor conformation. Furthermore, by mapping the GPCR-p11 interactome using a multiplexed suspension bead array (SBA) of 211 receptors, we identified more than two dozen high-confidence physical interactors across diverse GPCR signaling families. We define the functional significance of these interactions by focusing on a novel SBA screening hit, the protease-activated receptor 2 (PAR2). Transcriptomic fingerprinting and signaling assays in p11-knockout cells reveal that p11 acts as an amplifier of endogenous PAR2 signaling. PAR2 and p11 are specifically coexpressed in vivo in a subset of sensory neurons, and p11-deficient mice exhibit a blunted PAR2-mediated inflammatory response. Our results establish p11 as a widespread, activity-dependent modulator of GPCR-mediated signaling outcomes across diverse physiological processes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.",
    "Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden.",
    "Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA.",
    "Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA.",
    "Department of Medicine Solna, Division of Immunology and Respiratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.",
    "Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.",
    "Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.",
    "Basic and Clinical Neuroscience, King’s College London, London, UK."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Marcus Saarinen",
      "orcid": "0000-0001-9019-8396"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ilana B. Kotliar",
      "orcid": "0000-0001-9533-4828"
    },
    {
      "affs": [
        0
      ],
      "name": "Inga Höffkes"
    },
    {
      "affs": [
        0
      ],
      "name": "Niclas Branzell",
      "orcid": "0009-0009-3472-6903"
    },
    {
      "affs": [
        0
      ],
      "name": "Carl-Fredrik Bowin",
      "orcid": "0000-0001-9090-9493"
    },
    {
      "affs": [
        1
      ],
      "name": "Leo Dahl",
      "orcid": "0000-0003-1492-3052"
    },
    {
      "affs": [
        0
      ],
      "name": "Elisa Da Silva",
      "orcid": "0009-0006-0105-2402"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Vassilis Glaros"
    },
    {
      "affs": [
        0
      ],
      "name": "Alonso Abney",
      "orcid": "0000-0002-0164-8314"
    },
    {
      "affs": [
        1
      ],
      "name": "Annika Bendes",
      "orcid": "0000-0001-9329-2353"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Taras Kreslavsky",
      "orcid": "0000-0002-6672-1914"
    },
    {
      "affs": [
        1
      ],
      "name": "Jochen M. Schwenk",
      "orcid": "0000-0001-8141-8449"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Thomas P. Sakmar",
      "orcid": "0000-0002-2836-8953"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Per Svenningsson",
      "orcid": "0000-0001-6727-3802"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2qt2kzch6wsqw.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeg6567",
  "fulltext_url": null,
  "id": "2qt2kzch6wsqw",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeg6567",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7214906430",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/2qt2kzch6wsqw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeg6567",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeg6567"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Systematic identification of p11 as a signaling modulator across the GPCRome",
  "title_text": "Systematic identification of p11 as a signaling modulator across the GPCRome",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/2qt2kzch6wsqw",
  "venue": "Science Advances",
  "versions": []
}