Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-kinase/Akt pathway

R. Swart, I. K. Ruf, J. Sample, R. Longnecker

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is expressed on the membranes of B lymphocytes and blocks B-cell receptor (BCR) signaling in EBV-transformed B lymphocytes in vitro. The phosphotyrosine motifs at positions 74 or 85 and 112 within the LMP2A amino-terminal domain are essential for the LMP2A-mediated block of B-cell signal transduction. In vivo studies indicate that LMP2A allows B-cell survival in the absence of normal BCR signals. A possible role for Akt in the LMP2A-mediated B-cell survival was investigated. The protein kinase Akt is a crucial regulator of cell survival and is activated within B lymphocytes upon BCR cross-linking. LMP2A expression resulted in the constitutive phosphorylation of Akt, and this LMP2A effect is dependent on phosphatidylinositol 3-kinase activity. In addition, recruitment of Syk and Lyn protein tyrosine kinases (PTKs) to tyrosines 74 or 85 and 112, respectively, are critical for LMP2A-mediated Akt phosphorylation. However, the ability of LMP2A to mediate a survival phenotype downstream of Akt could not be detected in EBV-negative Akata cells. This would indicate that LMP2A is not responsible for EBV-dependent Burkitt's lymphoma cell survival.

Original languageEnglish (US)
Pages (from-to)10838-10845
Number of pages8
JournalJournal of virology
Volume74
Issue number22
DOIs
StatePublished - 2000

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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