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Our results show that VAF347 enhanced RA\u2010induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src\u2010family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c\u2010Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA\u2010induced expression of AhR, Lyn, Vav1, and c\u2010Cbl as well as p47<jats:sup>phox<\/jats:sup>. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c\u2010Cbl, CD38, and with pS259c\u2010Raf and AhR interaction with c\u2010Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub>, VAF347 promotes RA\u2010induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c\u2010Cbl, AhR, and Fgr.<\/jats:p>","DOI":"10.1016\/j.fob.2015.04.002","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T06:17:08Z","timestamp":1428733028000},"page":"308-318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The AhR agonist VAF347 augments retinoic acid\u2010induced differentiation in leukemia cells"],"prefix":"10.1002","volume":"5","author":[{"given":"Christopher N.","family":"Ibabao","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodica P.","family":"Bunaciu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanna M.W.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,8]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_8_2_1","DOI":"10.1182\/blood-2002-02-0632"},{"doi-asserted-by":"publisher","key":"e_1_2_8_3_1","DOI":"10.1093\/toxsci\/kft128"},{"doi-asserted-by":"publisher","key":"e_1_2_8_4_1","DOI":"10.1016\/j.cbi.2009.10.019"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.1371\/journal.pone.0013831"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1093\/carcin\/bgt083"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1158\/0008-5472.CAN-10-2299"},{"doi-asserted-by":"publisher","key":"e_1_2_8_8_1","DOI":"10.1038\/nature05683"},{"doi-asserted-by":"publisher","key":"e_1_2_8_9_1","DOI":"10.1515\/hsz-2012-0340"},{"doi-asserted-by":"publisher","key":"e_1_2_8_10_1","DOI":"10.1186\/1476-4598-12-39"},{"doi-asserted-by":"publisher","key":"e_1_2_8_11_1","DOI":"10.1016\/j.humimm.2012.05.002"},{"doi-asserted-by":"publisher","key":"e_1_2_8_12_1","DOI":"10.4049\/jimmunol.0802997"},{"doi-asserted-by":"publisher","key":"e_1_2_8_13_1","DOI":"10.1016\/j.stem.2009.04.011"},{"doi-asserted-by":"publisher","key":"e_1_2_8_14_1","DOI":"10.1371\/journal.pone.0019358"},{"doi-asserted-by":"publisher","key":"e_1_2_8_15_1","DOI":"10.1038\/leu.2011.390"},{"doi-asserted-by":"publisher","key":"e_1_2_8_16_1","DOI":"10.3109\/10428194.2011.603449"},{"doi-asserted-by":"publisher","key":"e_1_2_8_17_1","DOI":"10.1158\/0008-5472.CAN-08-1058"},{"doi-asserted-by":"publisher","key":"e_1_2_8_18_1","DOI":"10.1177\/153857440604000108"},{"key":"e_1_2_8_19_1","first-page":"103","article-title":"Expression of activated RAF accelerates cell differentiation and RB protein down-regulation but not hypophosphorylation","volume":"65","author":"Yen A.","year":"1994","journal-title":"Eur. 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