{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:39:37Z","timestamp":1792132777477,"version":"4.4.0"},"reference-count":81,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"743","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:p>\n                    The integrin lymphocyte function\u2013associated antigen 1 (LFA-1) helps to coordinate the migration, adhesion, and activation of T cells through interactions with intercellular adhesion molecule 1 (ICAM-1) and ICAM-2. LFA-1 is activated during the engagement of chemokine receptors and the T cell receptor (TCR) through inside-out signaling, a process that is partially mediated by phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol 3,4,5-trisphosphate (PIP\n                    <jats:sub>3<\/jats:sub>\n                    ). To evaluate potential roles of PI3K in LFA-1 activation, we designed a library of CRISPR\/single guide RNAs targeting known and potential PIP\n                    <jats:sub>3<\/jats:sub>\n                    -binding proteins and screened for effects on the ability of primary mouse T cells to bind to ICAM-1. We identified multiple proteins that regulated the binding of LFA-1 to ICAM-1, including the Rap1 and Ras GTPase-activating protein RASA3. We found that RASA3 suppressed LFA-1 activation in T cells, that its expression was rapidly reduced upon T cell activation, and that its activity was inhibited by PI3K. Loss of RASA3 in T cells led to increased Rap1 activation, defective lymph node entry and egress, and impaired responses to T-dependent immunization in mice. Our results reveal a critical role for RASA3 in T cell migration, homeostasis, and function.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.abl9169","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:56:36Z","timestamp":1658238996000},"source":"Crossref","is-referenced-by-count":39,"title":["A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1\u2013mediated adhesion in T cells"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-9451","authenticated-orcid":true,"given":"Kristoffer H.","family":"Johansen","sequence":"first","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."},{"name":"Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK."},{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA."},{"name":"Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-3302","authenticated-orcid":true,"given":"Dominic P.","family":"Golec","sequence":"additional","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5931-6075","authenticated-orcid":true,"given":"Bonnie","family":"Huang","sequence":"additional","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."},{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7819-5333","authenticated-orcid":true,"given":"Chung","family":"Park","sequence":"additional","affiliation":[{"name":"B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-3614","authenticated-orcid":true,"given":"Julie H.","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Preite","sequence":"additional","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."},{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Cannons","sequence":"additional","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."},{"name":"National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Gar\u00e7on","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-6433","authenticated-orcid":true,"given":"Edward C.","family":"Schrom","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-8486","authenticated-orcid":true,"given":"Christina J. F.","family":"Courr\u00e8ges","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-8900","authenticated-orcid":true,"given":"Tibor Z.","family":"Veres","sequence":"additional","affiliation":[{"name":"Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-5062","authenticated-orcid":true,"given":"James","family":"Harrison","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, 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