{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:54:55Z","timestamp":1790794495624,"version":"4.1.0"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"40","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM136640"],"award-info":[{"award-number":["T32 GM136640"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swedish Research Council","award":["2024-04352"],"award-info":[{"award-number":["2024-04352"]}],"id":[{"id":"https:\/\/ror.org\/03zttf063","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Robertson Therapeutic Development Fund"},{"name":"The Alexander Mauro Fellowship"},{"name":"Denise and Michael Kellen Foundation","award":["the Kellen Women in Science Entrepreneurship Fund"],"award-info":[{"award-number":["the Kellen Women in Science Entrepreneurship Fund"]}]},{"name":"The Danica Foundation"},{"name":"RED Postdoctoral Fellowship"},{"name":"Karolinska Institute KID program","id":[{"id":"https:\/\/ror.org\/056d84691","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wallenberg AI"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:p>\n                    The microprotein p11 (\n                    <jats:italic toggle=\"yes\">S100A10<\/jats:italic>\n                    ) 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\u2013coupled receptor (GPCR)\u2013mediated 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.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg6567","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:26Z","timestamp":1790791106000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Systematic identification of p11 as a signaling modulator across the GPCRome"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9019-8396","authenticated-orcid":true,"given":"Marcus","family":"Saarinen","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."},{"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9533-4828","authenticated-orcid":true,"given":"Ilana B.","family":"Kotliar","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA."},{"name":"Tri-Institutional PhD Program in Chemical Biology, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"H\u00f6ffkes","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3472-6903","authenticated-orcid":true,"given":"Niclas","family":"Branzell","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9090-9493","authenticated-orcid":true,"given":"Carl-Fredrik","family":"Bowin","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-3052","authenticated-orcid":true,"given":"Leo","family":"Dahl","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0105-2402","authenticated-orcid":true,"given":"Elisa","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Glaros","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Division of Immunology and Respiratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-8314","authenticated-orcid":true,"given":"Alonso","family":"Abney","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9329-2353","authenticated-orcid":true,"given":"Annika","family":"Bendes","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6672-1914","authenticated-orcid":true,"given":"Taras","family":"Kreslavsky","sequence":"additional","affiliation":[{"name":"Department of Medicine Solna, Division of Immunology and Respiratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden."},{"name":"Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-8449","authenticated-orcid":true,"given":"Jochen M.","family":"Schwenk","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2836-8953","authenticated-orcid":true,"given":"Thomas P.","family":"Sakmar","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology and Signal Transduction, The Rockefeller University, New York, NY, USA."},{"name":"Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6727-3802","authenticated-orcid":true,"given":"Per","family":"Svenningsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."},{"name":"Basic and Clinical Neuroscience, King\u2019s College London, London, 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