{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:28:15Z","timestamp":1791221295469,"version":"4.1.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,1,30]]},"abstract":"<jats:p>\n                    The Wiskott\u2013Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for T cell activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) in T cells and that WASp, SNX9, p85, and CD28 colocalize within clathrin-containing endocytic vesicles after TCR\/CD28 costimulation. SNX9, implicated in clathrin-mediated endocytosis, binds WASp via its SH3 domain and uses its PX domain to interact with the phosphoinositol 3-kinase regulatory subunit p85 and product, phosphoinositol (3,4,5)P\n                    <jats:sub>3<\/jats:sub>\n                    . The data reveal ligation-induced CD28 endocytosis to be clathrin- and phosphoinositol 3-kinase-dependent and TCR\/CD28-evoked CD28 internalization and NFAT activation to be markedly enhanced by SNX9 overexpression, but severely impaired by expression of an SNX9 mutant (SNX9\u0394PX) lacking p85-binding capacity. CD28 endocytosis and CD28-evoked actin polymerization also are impaired in WASp-deficient T cells. These findings suggest that SNX9 couples WASp to p85 and CD28 so as to link CD28 engagement to its internalization and to WASp-mediated actin remodeling required for CD28 cosignaling. Thus, the WASp\/SNX9\/p85\/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0610543104","type":"journal-article","created":{"date-parts":[[2007,1,22]],"date-time":"2007-01-22T20:58:06Z","timestamp":1169499486000},"page":"1593-1598","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":91,"title":["Interaction of the Wiskott\u2013Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells"],"prefix":"10.1073","volume":"104","author":[{"given":"Karen","family":"Badour","sequence":"first","affiliation":[{"name":"*Departments of Medicine, Immunology, Medical Genetics, and Microbiology, University of Toronto, Toronto General Hospital and Samuel Lunenfeld Research Institutes, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K. 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