Latent Membrane Protein 2 (LMP2)

Curr Top Microbiol Immunol. 2015:391:151-80. doi: 10.1007/978-3-319-22834-1_5.

Abstract

LMP2A is an EBV-encoded protein with three domains: (a) an N-terminal cytoplasmic domain, which has PY motifs that bind to WW domain-containing E3 ubiquitin ligases and an ITAM that binds to SH2 domain-containing proteins, (b) a transmembrane domain with 12 transmembrane segments that localizes LMP2A in cellular membranes, and (c) a 27-amino acid C-terminal domain which mediates homodimerization and heterodimerization of LMP2 protein isoforms. The most prominent two isoforms of the protein are LMP2A and LMP2B. The LMP2B isoform lacks the 19-amino acid N-terminal domain found in LMP2A, which modulates cellular signaling resulting in a baseline activation of B cells and degradation of cellular kinases leading to the downregulation of normal B cell signaling pathways. These two seemingly contradictory processes allow EBV to establish and maintain latency. LMP2 is expressed in many EBV-associated malignancies. While its antigenic properties may be useful in developing LMP2-specific immunity, the LMP2A N-terminal motifs also provide a basis to target LMP2A-modulated cellular kinases for the development of treatment strategies.

Keywords: Epstein-Barr virus; LMP2A; Lyn; Signal transduction; Syk.

Publication types

  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / virology*
  • Herpesvirus 4, Human / chemistry
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Protein Isoforms
  • Viral Matrix Proteins