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Cross\u2010linking of this activation antigen induces signaling events related to T cell activation. The proto\u2010oncogene product Ras has been reported to up\u2010regulate CD69. However, which of the potential effectors of Ras induces the expression of CD69 has remained unclear. Using transient transfection, we have shown a constitutively active form of the serine\/threonine kinase Raf\u20101 to be sufficient to induce CD69 expression in human Jurkat T cells. Raf\u20101 was further shown to be necessary for PMA\u2010induced CD69 expression, since transfection of a dominant inhibitory form of Raf\u20101 blocked the up\u2010regulation of CD69 by PMA. In addition, studies with the calcium ionophore ionomycin identified a previously uncharacterized pathway regulating the expression of CD69 in T cells. Elevation of intracellular calcium induced the expression of CD69 in both Jurkat cells and peripheral blood T cells. This effect was sensitive to the immunosuppressive drug cyclosporin A, indicating that calcium\u2010induced CD69 expression is mediated by the protein phosphatase calcineurin. Taken together, these results define Raf\u20101 as the major signaling mediator of CD69 expression in T cells and suggest that multiple mechanisms exist to regulate the level of CD69 expression following TCR stimulation.<\/jats:p>","DOI":"10.1002\/eji.1830251203","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T23:36:53Z","timestamp":1172792213000},"page":"3215-3221","source":"Crossref","is-referenced-by-count":33,"title":["Raf\u20101 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells"],"prefix":"10.1002","volume":"25","author":[{"given":"David A.","family":"Taylor\u2010Fishwick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey N.","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90334-4"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.55.2.265"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.63.070194.005145"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90193-7"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.5530120502"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.11.4920"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240735"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.4049\/jimmunol.142.6.1854","volume":"142","author":"Testi R.","year":"1989","journal-title":"J. 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