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

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8806-8814
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number13
DOIs
Publication statusPublished - Mar 31 2006
Externally publishedYes

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Human Herpesvirus 4
Viruses
Protein-Tyrosine Kinases
Cell Movement
Membrane Proteins
Epithelial Cells
Chemical activation
Tyrosine
Tumors
Immunoreceptor Tyrosine-Based Activation Motif
Syk Kinase
B-Lymphocytes
Gammaretrovirus
Cells
Breast Neoplasms
Neoplasms
Confocal microscopy
Confocal Microscopy
Small Interfering RNA
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. / Lu, Jean; Lin, Wan Hsin; Chen, Shao Yin; Longnecker, Richard; Tsai, Shu Chun; Chen, Chi Long; Tsai, Ching Hwa.

In: Journal of Biological Chemistry, Vol. 281, No. 13, 31.03.2006, p. 8806-8814.

Research output: Contribution to journalArticle

Lu, Jean ; Lin, Wan Hsin ; Chen, Shao Yin ; Longnecker, Richard ; Tsai, Shu Chun ; Chen, Chi Long ; Tsai, Ching Hwa. / Syk tyrosine kinase mediates Epstein-Barr virus latent membrane protein 2A-induced cell migration in epithelial cells. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 13. pp. 8806-8814.
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