Chou Y.-C.Lin S.-J.Lu J.TE-HUEI YEHChen C.-L.Weng P.-L.Lin J.-H.MING YAOCHING-HWA TSAI2021-01-052021-01-0520110006-4971https://www.scopus.com/inward/record.uri?eid=2-s2.0-80051554138&doi=10.1182%2fblood-2011-02-335448&partnerID=40&md5=11f8c44624e248a9a05ff99514490ce0https://scholars.lib.ntu.edu.tw/handle/123456789/537974EBV, an oncogenic human herpesvirus, can transform primary B lymphocytes into immortalized lymphoblastoid cell lines (LCLs) through multiple regulatory mechanisms. However, the involvement of protein tyrosine kinases in the infinite proliferation of B cells is not clear. In this study, we performed kinase display assays to investigate this subject and identified a specific cellular target, Recepteur d'Origine Nantais (RON) tyrosine kinase, expressed in LCLs but not in primary B cells. Furthermore, we found that latent membrane protein 1 (LMP1), an important EBV oncogenic protein, enhanced RON expression through its C-terminal activation region-1 (CTAR1) by promoting NF-κB binding to the RON promoter. RON knockdown decreased the proliferation of LCLs, and transfection with RON compensated for the growth inhibition caused by knockdown of LMP1. Immunohistochemical analysis revealed a correlation between LMP1 and RON expression in biopsies from posttransplantation lymphoproliferative disorder (PTLD), suggesting that LMP1-induced RON expression not only is essential for the growth of LCLs but also may contribute to the pathogenesis of EBV-associated PTLD. Our study is the first to reveal the impact of RON on the proliferation of transformed B cells and to suggest that RON may be a novel therapeutic target for EBV-associated lymphoproliferative diseases. ? 2011 by The American Society of Hematology.[SDGs]SDG33 (4 methylphenylsulfonyl) 2 propenenitrile; immunoglobulin enhancer binding protein; latent membrane protein 1; protein tyrosine kinase; recepteur d origine natais enzyme; unclassified drug; adult; article; B lymphocyte; carboxy terminal sequence; cell proliferation; child; clinical article; drug targeting; Epstein Barr virus; Epstein Barr virus infection; female; human; human cell; human tissue; immunohistochemistry; lymph node biopsy; lymphoblastoid cell; lymphoproliferative disease; male; posttransplantation lymphoproliferative disorder; preschool child; priority journal; protein binding; protein expression; school child; signal transduction; transplantationjournal article10.1182/blood-2011-02-335448216595462-s2.0-80051554138