{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:31:57Z","timestamp":1791322317060,"version":"4.3.1"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6,18]]},"abstract":"<jats:p>The product of the protooncogene Vav1 participates in multiple signaling pathways and is a critical regulator of antigen\u2013receptor signaling in B and T lymphocytes, but its role during in vivo natural killer (NK) cell differentiation is not known. Here we have studied NK cell development in Vav1\u2212\/\u2212 mice and found that, in contrast to T and NK-T cells, the absolute numbers of phenotypically mature NK cells were not reduced. Vav1\u2212\/\u2212 mice produced normal amounts of interferon (IFN)-\u03b3 in response to Listeria monocytogenes and controlled early infection but showed reduced tumor clearance in vivo. In vitro stimulation of surface receptors in Vav1\u2212\/\u2212 NK cells resulted in normal IFN-\u03b3 production but reduced tumor cell lysis. Vav1 was found to control activation of extracellular signal-regulated kinases and exocytosis of cytotoxic granules. In contrast, conjugate formation appeared to be only mildly affected, and calcium mobilization was normal in Vav1\u2212\/\u2212 NK cells. These results highlight fundamental differences between proximal signaling events in T and NK cells and suggest a functional dichotomy for Vav1 in NK cells: a role in cytotoxicity but not for IFN-\u03b3 production.<\/jats:p>","DOI":"10.1084\/jem.193.12.1413","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1413-1424","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Functional Dichotomy in Natural Killer Cell Signaling"],"prefix":"10.1084","volume":"193","author":[{"given":"Francesco","family":"Colucci","sequence":"first","affiliation":[{"name":"aLaboratory for Cytokines and Lymphoid Development, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Rosmaraki","sequence":"additional","affiliation":[{"name":"aLaboratory for Cytokines and Lymphoid Development, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Bregenholt","sequence":"additional","affiliation":[{"name":"aLaboratory for Cytokines and Lymphoid Development, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine I.","family":"Samson","sequence":"additional","affiliation":[{"name":"aLaboratory for Cytokines and Lymphoid Development, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Di Bartolo","sequence":"additional","affiliation":[{"name":"bLaboratory for Molecular Immunology, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Turner","sequence":"additional","affiliation":[{"name":"cThe Babraham Institute, Cambridge CB2 4AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Vanes","sequence":"additional","affiliation":[{"name":"dThe National Institute for Medical Research, London NW7 1AA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Tybulewicz","sequence":"additional","affiliation":[{"name":"dThe National Institute for Medical Research, London NW7 1AA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Di Santo","sequence":"additional","affiliation":[{"name":"aLaboratory for Cytokines and Lymphoid Development, Pasteur Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,6,18]]},"reference":[{"key":"2023072509382576800_R1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0167-5699(97)01037-2","article-title":"Views on Vav","volume":"18","author":"Collins","year":"1997","journal-title":"Immunol. 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