Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth

J Biol Chem. 1998 Oct 16;273(42):27548-56. doi: 10.1074/jbc.273.42.27548.

Abstract

Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappaB and AP-1 through a TNF receptor-associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-related proteins derived from an expressed sequence tag data base. One of these, which we designated HVEM-L, specifically bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with soluble and membrane forms of both receptor and ligand. HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid protein. A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappaB-dependent transcription.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Gene Expression Regulation
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / pharmacology
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • HT29 Cells / drug effects
  • Humans
  • Ligands
  • Lymphocyte Culture Test, Mixed
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / pharmacology
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Protein Binding
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 14
  • Receptors, Virus / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / drug effects
  • Tissue Distribution
  • Transcription Factor AP-1 / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Growth Inhibitors
  • Growth Substances
  • Ligands
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 14
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • TNFRSF14 protein, human
  • TNFSF14 protein, human
  • Transcription Factor AP-1
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha

Associated data

  • GENBANK/AF064090