{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:59:45Z","timestamp":1791295185155,"version":"4.1.0"},"reference-count":52,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,4,7]]},"abstract":"<jats:p>Ewing\u2019s sarcoma-associated transcript 2 (EAT-2) is an Src homology 2 domain-containing intracellular adaptor related to signaling lymphocytic activation molecule (SLAM)\u2013associated protein (SAP), the X-linked lymphoproliferative gene product. Both EAT-2 and SAP are expressed in natural killer (NK) cells, and their combined expression is essential for NK cells to kill abnormal hematopoietic cells. SAP mediates this function by coupling SLAM family receptors to the protein tyrosine kinase Fyn and the exchange factor Vav, thereby promoting conjugate formation between NK cells and target cells. We used a variety of genetic, biochemical, and imaging approaches to define the molecular and cellular mechanisms by which EAT-2 controls NK cell activation. We found that EAT-2 mediates its effects in NK cells by linking SLAM family receptors to phospholipase C\u03b3, calcium fluxes, and Erk kinase. These signals are triggered by one or two tyrosines located in the carboxyl-terminal tail of EAT-2 but not found in SAP. Unlike SAP, EAT-2 does not enhance conjugate formation. Rather, it accelerates polarization and exocytosis of cytotoxic granules toward hematopoietic target cells. Hence, EAT-2 promotes NK cell activation by molecular and cellular mechanisms distinct from those of SAP. These findings explain the cooperative and essential function of these two adaptors in NK cell activation.<\/jats:p>","DOI":"10.1084\/jem.20132038","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T01:27:25Z","timestamp":1396315645000},"page":"727-742","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase C\u03b3, Ca++, and Erk, leading to granule polarization"],"prefix":"10.1084","volume":"211","author":[{"given":"Luis-Alberto","family":"P\u00e9rez-Quintero","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Oncology, Clinical Research Institute of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada 1"},{"name":"Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec H3G 1Y6, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Roncagalli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Clinical Research Institute of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada 1"},{"name":"Department of Medicine, University of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H3T 1J4, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaijian","family":"Guo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Clinical Research Institute of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada 1"},{"name":"Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec H3G 1Y6, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Latour","sequence":"additional","affiliation":[{"name":"INSERM UMR 1163, Laboratory of Lymphocyte Activation and Susceptibility to EBV, Universit\u00e9 Paris Descartes-Sorbonne Paris Cit\u00e9, Institut Imagine, 75743 Paris, France 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Davidson","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Clinical Research Institute of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Veillette","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology, Clinical Research Institute of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H2W 1R7, Canada 1"},{"name":"Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec H3G 1Y6, Canada 2"},{"name":"Department of Medicine, University of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec H3T 1J4, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,3,31]]},"reference":[{"key":"2023072602132639400_bib1","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1182\/blood-2004-07-2731","article-title":"Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative disease gene Sap","volume":"106","author":"Al-Alem","year":"2005","journal-title":"Blood."},{"key":"2023072602132639400_bib2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1084\/jem.194.3.235","article-title":"NTB-A, a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus\u2013infected B cells in X-linked lymphoproliferative disease","volume":"194","author":"Bottino","year":"2001","journal-title":"J. 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