Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells

Jean Lu, Wan Hsin Lin, Shao Yin Chen, Richard Longnecker, Shu Chun Tsai, Chi Long Chen, Ching Hwa Tsai

研究成果: 雜誌貢獻文章同行評審

83 引文 斯高帕斯(Scopus)

摘要

Although spleen tyrosine kinase (Syk) is known to be important in hematopoietic cell development, the roles of Syk in epithelial cells have not been well studied. Limited data suggest that Syk plays alternate roles in carcinogenesis under different circumstances. In breast cancer, Syk has been suggested to be a tumor suppressor. In contrast, Syk is essential for murine mammary tumor virus-mediated transformation. However, the roles of Syk in tumor migration are still largely unknown. Nasopharyngeal carcinoma, an unusually highly metastatic tumor, expresses Epstein-Barr virus LMP2A (latent membrane protein 2A) in most clinical specimens. Previously, we demonstrated LMP2A triggers epithelial cell migration. LMP2A contains an immunoreceptor tyrosine-based activation motif, which is important for Syk kinase activation in B cells. In this study, we explored whether Syk is important for LMP2A-mediated epithelial cell migration. We demonstrate that LMP2A expression can activate endogenous Syk activity. The activation requires the tyrosine residues in LMP2A ITAM but not YEEA motif, which is important for Syk activation by Lyn in B cells. LMP2A interacts with Syk as demonstrated by coimmunoprecipitation and confocal microscopy. Furthermore, LMP2A-induced cell migration is inhibited by a Syk inhibitor and short interfering RNA. Tyrosines 74 and 85 in the LMP2A immunoreceptor tyrosine-based activation motif are essential for both Syk activation and LMP2A-mediated cell migration, indicating the involvement of Syk in LMP2A-triggered cell migration. The LMP2A-Syk pathway may provide suitable drug targets for treatment of nasopharyngeal carcinoma.

原文英語
頁(從 - 到)8806-8814
頁數9
期刊Journal of Biological Chemistry
281
發行號13
DOIs
出版狀態已發佈 - 3月 31 2006

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學

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