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Cross\u2010linking Fc\u03b3RIIIA initiates the rapid tyrosine phosphorylation of multiple substrates including the \u03b6, subunit and causes subsequent cell activation and antibody\u2010dependent cellular cytotoxicity (ADCC). The subunits of the Fc\u03b3RIIIA complex lack intrinsic protein tyrosine kinase (PTK) activity, suggesting that receptor\u2010induced tyrosine phosphorylation events are mediated by a nonreceptor PTK. We report here that the human Fc\u03b3RIIIA is complexed with p56<jats:italic><jats:sup>lck<\/jats:sup><\/jats:italic>, a <jats:italic>src<\/jats:italic>\u2010family PTK previously found associated with the CD4 and CD8 receptors on T cells. Upon engagement of the CD16 receptor, p56<jats:italic><jats:sup>lck<\/jats:sup><\/jats:italic> is rapidly (within 30 s) and transiently phosphorylated on tyrosine residues. Several Fc\u03b3RIIIA\u2010associated proteins are identified in immune complex kinase assays including the TCR\u2010\u03b6, subunit, a p70\u201390 \u03b6\u2010associated protein (ZAP), p50a (acidic) and p50b (basic), and p56<jats:italic><jats:sup>lck<\/jats:sup><\/jats:italic>. We demonstrate that the <jats:italic>src<\/jats:italic>\u2010family protein tyrosine kinase inhibitor, herbimycin A, blocks increased intracellular calcium levels and ADCC caused by CD16 cross\u2010linking on NK3.3 cells. Likewise cross\u2010linking CD16 with the protein tyrosine phosphatase CD45, abrogates CD16\u2010induced calcium mobilization. These data suggest that p56<jats:italic><jats:sup>lck<\/jats:sup><\/jats:italic> is physically associated with Fc\u03b3RIIIA(CD16) and functions to mediate signaling events related to the control of NK cellular cytotoxicity.<\/jats:p>","DOI":"10.1002\/eji.1830231017","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T18:36:00Z","timestamp":1172774160000},"page":"2488-2497","source":"Crossref","is-referenced-by-count":38,"title":["Association of the p56<sup>lck<\/sup> protein tyrosine kinase with the FC\u03b3RIIIA\/CD16 complex in human natural killer cells"],"prefix":"10.1002","volume":"23","author":[{"given":"J.","family":"Catherine Cone","sequence":"first","affiliation":[]},{"given":"Yiling","family":"Lu","sequence":"additional","affiliation":[]},{"given":"James M.","family":"Trevillyan","sequence":"additional","affiliation":[]},{"given":"Jay M.","family":"Bjorndahl","sequence":"additional","affiliation":[]},{"given":"Catherine A.","family":"Phillips","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.06.040188.001343"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113891"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60664-1"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1182\/blood.V75.6.1211.1211","volume":"75","author":"Huizinga T. 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