The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways

Immunity. 2002 Oct;17(4):525-35. doi: 10.1016/s1074-7613(02)00423-5.

Abstract

The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • I-kappa B Kinase
  • Lymphotoxin beta Receptor
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Biological
  • NF-kappa B / metabolism*
  • NF-kappa B p52 Subunit
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*

Substances

  • LTBR protein, human
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • NF-kappa B
  • NF-kappa B p52 Subunit
  • Receptors, Tumor Necrosis Factor
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • Chuk protein, mouse
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • NF-kappa B kinase