Tumor necrosis factor - α Activates the sphingomyelin signal transduction pathway in a cell-free system Academic Article uri icon

Overview

MeSH Major

  • Ceramides
  • Protein Kinases
  • Receptors, Cell Surface
  • Signal Transduction
  • Sphingomyelin Phosphodiesterase
  • Sphingomyelins
  • Tumor Necrosis Factor-alpha

abstract

  • The mechanism of tumor necrosis factor (TNF)-alpha signaling is unknown. TNF-alpha signaling may involve sphingomyelin hydrolysis to ceramide by a sphingomyelinase and stimulation of a ceramide-activated protein kinase. In a cell-free system, TNF-alpha induced a rapid reduction in membrane sphingomyelin content and a quantitative elevation in ceramide concentrations. Ceramide-activated protein kinase activity also increased. Kinase activation was mimicked by addition of sphingomyelinase but not by phospholipases A2, C, or D. Reconstitution of this cascade in a cell-free system demonstrates tight coupling to the receptor, suggesting this is a signal transduction pathway for TNF-alpha.

publication date

  • March 27, 1992

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 1313189

Additional Document Info

start page

  • 1715

end page

  • 8

volume

  • 255

number

  • 5052