{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:43:10Z","timestamp":1792172590875,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T00:00:00Z","timestamp":1343952000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> is a transmembrane receptor mainly expressed on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells and <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells. Engagement of <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> with its ligands can trigger a cytotoxic response. It has been shown that tumor cells deliver soluble <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> ligands as a mechanism of immune evasion through the downregulation of surface\u2010expressed <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>. These ligands may be also secreted in microvesicles and regulate <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\u2010cell function, but the existence of alternative mechanisms has not been explored. In this study, we describe that <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> activation inhibits <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\u2010cell chemotaxis toward a <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 gradient. Costimulation of the inhibitory receptor <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> rescues <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\u2010cell migration rates. Thus, the balance of <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> activation may determine the migratory ability of <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells. Furthermore, our data indicated that <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> cross\u2010linking induces the activation of the <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ho <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ases <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ac1 and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>dc42, while <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>hoA activity is decreased. Pharmacological inhibition of the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>dc42 effectors Wiskott\u2010Aldrich syndrome protein (WASp)\/N\u2010WASp, and the reduction of their levels using <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> interference partially abolished <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\u2010mediated impairment of cell migration, suggesting a pivotal role of <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>dc42 in the regulation of <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content>\u2010cell migration by <jats:styled-content style=\"fixed-case\">NKG<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content> activation. Therefore, our results provide a new mechanism that may contribute to the immune response or evasion in tumors.<\/jats:p>","DOI":"10.1002\/eji.201142070","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T07:05:32Z","timestamp":1337065532000},"page":"2142-2151","source":"Crossref","is-referenced-by-count":10,"title":["Wiskott\u2010Aldrich syndrome protein (WASp) and N\u2010WASp are involved in the regulation of NK\u2010cell migration upon NKG2D activation"],"prefix":"10.1002","volume":"42","author":[{"given":"Esther","family":"Serrano\u2010Pertierra","sequence":"first","affiliation":[{"name":"Immunology Department Hospital Universitario Central de Asturias  Oviedo Asturias Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Cernuda\u2010Moroll\u00f3n","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital Universitario Central de Asturias  Oviedo Asturias Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez\u2010Larrea","sequence":"additional","affiliation":[{"name":"Immunology Department Hospital Universitario Central de Asturias  Oviedo Asturias Spain"},{"name":"Fundaci\u00f3n Renal \u201cI\u00f1igo Alvarez de Toledo\u201d  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115526"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01673-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2922005cm6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.02.004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2007.02652.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-0060-9"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-008-0585-3"},{"key":"e_1_2_7_9_1","first-page":"1389","article-title":"Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia","volume":"102","author":"Salih H. 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