{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:00:39Z","timestamp":1790787639434,"version":"4.1.0"},"reference-count":88,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["PO1 A1091580"],"award-info":[{"award-number":["PO1 A1091580"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["Center for Geometrically Engineered Cellular Systems"],"award-info":[{"award-number":["Center for Geometrically Engineered Cellular Systems"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:p>\n                    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 PLC\u03b31 in the LAT protein condensate. Here, we describe detailed kinetic measurements examining how protein condensation of LAT regulates activation of PLC\u03b31 using a reconstituted membrane system. The results reveal that membrane recruitment of PLC\u03b31 is tightly controlled by the LAT phosphorylation state, with no measurable independent recruitment to PIP\n                    <jats:sub>2<\/jats:sub>\n                    or PIP\n                    <jats:sub>3<\/jats:sub>\n                    lipids via the PLC\u03b31 PH domains. We further observe PLC\u03b31 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 PLC\u03b31 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 PLC\u03b31 activation from a single TCR. These results suggest the LAT condensate facilitates both signal amplification and noise suppression in PLC\u03b31 activation through a bimodal switch affecting LAT phosphorylation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2614738123","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:13:32Z","timestamp":1790784812000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["LAT condensation gates PLC\u03b31 activation via bimodal LAT phosphorylation"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2838-835X","authenticated-orcid":false,"given":"He","family":"Ren","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1780-940X","authenticated-orcid":false,"given":"Hyun-Ro","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6700-2519","authenticated-orcid":false,"given":"Yannick A. 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Ren H.-R. Lee J. T. Groves Supplemental Data: LAT condensation gates PLC\u03b31 activation via bimodal LAT phosphorylation [Dataset]. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.19963430. 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