https://scholars.lib.ntu.edu.tw/handle/123456789/537974
標題: | Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation | 作者: | Chou Y.-C. Lin S.-J. Lu J. TE-HUEI YEH Chen C.-L. Weng P.-L. Lin J.-H. MING YAO CHING-HWA TSAI |
公開日期: | 2011 | 卷: | 118 | 期: | 5 | 起(迄)頁: | 1340-1349 | 來源出版物: | Blood | 摘要: | EBV, 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-80051554138&doi=10.1182%2fblood-2011-02-335448&partnerID=40&md5=11f8c44624e248a9a05ff99514490ce0 https://scholars.lib.ntu.edu.tw/handle/123456789/537974 |
ISSN: | 0006-4971 | DOI: | 10.1182/blood-2011-02-335448 | SDG/關鍵字: | 3 (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; transplantation |
顯示於: | 醫學系 |
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