Epstein-Barr virus latent membrane protein 2A (LMP2A) employs the SLP-65 signaling module

N. Engels, M. Merchant, R. Pappu, A. C. Chan, R. Longnecker, J. Wienands*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


In latently infected B lymphocytes, the Epstein-Barr virus (EBV) suppresses signal transduction from the antigen receptor through expression of the integral latent membrane protein 2A (LMP2A). At the same time, LMP2A triggers B cell survival by a yet uncharacterized maintenance signal that is normally provided by the antigen receptor. The molecular mechanisms are unknown as LMP2A-regulated signaling cascades have not been described so far. Using a novel mouse model we have identified the intracellular adaptor protein Src homology 2 (SH2) domain-containing leukocyte protein (SLP)-65 as a critical downstream effector of LMP2A in vivo. Biochemical analysis of the underlying signaling pathways revealed that EBV infection causes constitutive tyrosine phosphorylation of one of the two SLP-65 isoforms and complex formation between SLP-65 and the protooncoprotein CrkL (CT10 regulator of kinase like). This leads to antigen receptor-independent phosphorylation of Cbl (Casitas B lineage lymphoma) and C3G. In contrast, phospholipase C-γ2 (PLC-γ2) activation is completely blocked. Our data show that in order to establish a latent EBV infection, LMP2A selectively activates or represses SLP-65-regulated signaling pathways.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Aug 6 2001


  • Antigen receptor
  • B lymphocytes
  • Epstein-Barr virus
  • SLP-65
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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