{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:39:19Z","timestamp":1771612759130,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>B cell Ag receptor (BCR) cross-linking with anti-Ig Abs efficiently induces activation of latently infected EBV in some B cell lines, but not in others. The present study was aimed at defining the molecular mechanisms that determine the response to BCR-mediated EBV activation. Comparison of Burkitt\u2019s lymphoma-derived Akata, Mutu-I, and Daudi cells, which are representative responders and nonresponders to BCR-mediated EBV activation, respectively, indicated that three signaling pathways, phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK), were activated in anti-Ig-treated Akata and Mutu-I cells. However, in anti-Ig-treated Daudi cells PI3K was not activated, ERK was faintly activated, and p38 MAPK was constitutively phosphorylated irrespective of anti-Ig treatment. Restoration of PI3K activity with insulin-like growth factor 1 restored ERK and p38 MAPK pathways, and was accompanied by EBV activation in anti-Ig-treated Daudi cells. In contrast, a specific inhibitor for PI3K, wortmannin, inhibited EBV activation by anti-Ig Abs in Akata and Mutu-I cells. Transfection assays in EBV-negative Daudi cells revealed that PI3K activated a promoter for BZLF1, which is a switch of EBV activation from a latent infection, in the absence of other EBV products suggesting that the BZLF promoter was a target of BCR signaling, and that PI3K was important for BCR-mediated BZLF1 activation. These results indicate that the absence of PI3K impedes the progression of signals through the BCR and becomes a determinant of unresponsiveness to BCR-mediated EBV activation.<\/jats:p>","DOI":"10.4049\/jimmunol.172.3.1561","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:36Z","timestamp":1398028116000},"page":"1561-1566","source":"Crossref","is-referenced-by-count":38,"title":["Phosphatidylinositol 3-Kinase Is a Determinant of Responsiveness to B Cell Antigen Receptor-Mediated Epstein-Barr Virus Activation"],"prefix":"10.1093","volume":"172","author":[{"given":"Dai","family":"Iwakiri","sequence":"first","affiliation":[{"name":"Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenzo","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2026020211162114600_R1","first-page":"2575","volume-title":"Fields Virology","year":"2002"},{"key":"2026020211162114600_R2","first-page":"83","volume-title":"Proc. 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