The death domain kinase RIP mediates the TNF-induced NF-kappaB signal

Immunity. 1998 Mar;8(3):297-303. doi: 10.1016/s1074-7613(00)80535-x.

Abstract

The death domain serine/threonine kinase RIP interacts with the death receptors Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-kappaB activation. To define the physiologic role(s) that RIP plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice through homologous recombination. RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1-3 days of age. In contrast to a normal thymic anti-Fas response, rip-/- cells are highly sensitive to TNFalpha-induced cell death. Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a failure to activate the transcription factor NF-kappaB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / pathology
  • Animals
  • Apoptosis*
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cytokines
  • Failure to Thrive
  • Genes, Lethal
  • JNK Mitogen-Activated Protein Kinases
  • Lymphoid Tissue / pathology
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinases*
  • NF-kappa B / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Tumor Necrosis Factor-alpha / metabolism*
  • fas Receptor

Substances

  • Cytokines
  • NF-kappa B
  • Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Protein-Serine-Threonine Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases