Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation

Ya Ching Chou, Sue Jane Lin, Jean Lu, Te Huei Yeh, Chi Long Chen, Pei Lun Weng, Jiun Han Lin, Ming Yao, Ching Hwa Tsai

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1340-1349
Number of pages10
JournalBlood
Volume118
Issue number5
DOIs
Publication statusPublished - Aug 4 2011

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Cell proliferation
Human Herpesvirus 4
Viruses
Protein-Tyrosine Kinases
Membrane Proteins
B-Lymphocytes
Cell Proliferation
Cells
Cell Line
Lymphoproliferative Disorders
RON protein
Lymphocytes
Biopsy
Herpesviridae
Growth
Transfection
Assays
Phosphotransferases
Chemical activation
Display devices

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation. / Chou, Ya Ching; Lin, Sue Jane; Lu, Jean; Yeh, Te Huei; Chen, Chi Long; Weng, Pei Lun; Lin, Jiun Han; Yao, Ming; Tsai, Ching Hwa.

In: Blood, Vol. 118, No. 5, 04.08.2011, p. 1340-1349.

Research output: Contribution to journalArticle

Chou, YC, Lin, SJ, Lu, J, Yeh, TH, Chen, CL, Weng, PL, Lin, JH, Yao, M & Tsai, CH 2011, 'Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation', Blood, vol. 118, no. 5, pp. 1340-1349. https://doi.org/10.1182/blood-2011-02-335448
Chou, Ya Ching ; Lin, Sue Jane ; Lu, Jean ; Yeh, Te Huei ; Chen, Chi Long ; Weng, Pei Lun ; Lin, Jiun Han ; Yao, Ming ; Tsai, Ching Hwa. / Requirement for LMP1-induced RON receptor tyrosine kinase in Epstein-Barr virus-mediated B-cell proliferation. In: Blood. 2011 ; Vol. 118, No. 5. pp. 1340-1349.
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