{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:17:36Z","timestamp":1782346656434,"version":"3.54.5"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Red de Investigaci\u00f3n Renal"},{"name":"REDinREN","award":["RD 12\/0021"],"award-info":[{"award-number":["RD 12\/0021"]}]},{"name":"Spanish Fondo de Investigaciones Sanitarias-Fondos Fonds Europ\u00e9en de D\u00e9veloppement R\u00e9gional (FEDER) European Union","award":["PI12\/02587"],"award-info":[{"award-number":["PI12\/02587"]}]},{"name":"Severo Ochoa\u201d fellowship"},{"DOI":"10.13039\/501100008430","name":"FICYT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008430","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008430","name":"Clar\u00edn program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008430","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The activating receptor NKG2D is mainly expressed in NK cells and CD8+ T cells. NKG2D and CD28 recruit the p85 subunit of PI3K to propagate their signals through the YXXM signaling motif. The function of CD28 as a costimulatory molecule is well-established in T cells. Ligation of NKG2D on T cells costimulates TCR signaling, although the intracellular signaling pathways triggered by the two receptors may not be identical. In this study, we analyzed the function of the NKG2D receptor in human CD8+ T cell chemotaxis toward a CXCL12 gradient. We found that costimulation of the TCR together with CD28 or NKG2D impairs cell migration, although the signaling pathways responsible for this effect differ. Whereas the Rho GTPase Rac1 is activated upon TCR and costimulation via CD28 and NKG2D, the activity of Cdc42 is increased only upon CD3\/NKG2D activation. Moreover, knockdown of N-WASp expression with siRNA rescues migration rates after NKG2D-mediated costimulation but not after CD3\/CD28 activation. CD28- and NKG2D-mediated costimulation induces cofilin activation by dephosphorylation. Inhibition of N-WASp by wiskostatin further decreases phosphorylation levels of cofilin, although this effect is especially severe upon CD3\/NKG2D activation. Thus, our findings reveal new differences in the signaling pathways between CD28- and NKG2D-mediated costimulation in the regulation of cell chemotaxis in human CD8+ T cells.<\/jats:p>","DOI":"10.1189\/jlb.0613316","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T03:09:30Z","timestamp":1383102570000},"page":"487-495","source":"Crossref","is-referenced-by-count":11,"title":["NKG2D- and CD28-mediated costimulation regulate CD8+ T cell chemotaxis through different mechanisms: the role of Cdc42\/N-WASp"],"prefix":"10.1093","volume":"95","author":[{"given":"Esther","family":"Serrano-Pertierra","sequence":"first","affiliation":[{"name":"Immunology, Hospital Universitario Central de Asturias , Oviedo, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Cernuda-Moroll\u00f3n","sequence":"additional","affiliation":[{"name":"Neurology Departments, Hospital Universitario Central de Asturias , Oviedo, Asturias, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"L\u00f3pez-Larrea","sequence":"additional","affiliation":[{"name":"Immunology, Hospital Universitario Central de Asturias , Oviedo, Asturias, Spain"},{"name":"Fundaci\u00f3n Renal \u201c\u00cd\u00f1igo \u00c1lvarez de Toledo\u201d , Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,29]]},"reference":[{"key":"2023032709541977400_","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molmed.2008.02.004","article-title":"The NKG2D receptor: sensing stressed cells","volume":"14","author":"L\u00f3pez-Larrea","year":"2008","journal-title":"Trends Mo. 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