Identification of ceramide targets in interleukin-1 and tumor necrosis factor-alpha signaling in mesangial cells.
An increasing number of cell-surface receptors have been shown to trigger sphingomyelin turnover and generation of the lipid signaling molecule ceramide. Ceramide plays a role in mediating cellular responses as diverse as inflammation, differentiation, gene expression, growth suppression, and apoptosis. A radioiodinated, photoaffinity-labeling analog of ceramide ([125I]TID-ceramide) was used to identify downstream signaling targets of ceramide. Ceramide was found to bind specifically to and activate protein kinase c-Raf, leading to subsequent activation of the extracellular signal-regulated kinase (ERK) module in mesangial cells. We found also that ceramide binds to and differentially modulates the activity of distinct protein kinase C isoenzymes. These data are discussed in the context of interleukin 1beta-induced inflammatory gene expression in mesangial cells.
Pfeilschifter
J
J
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. Pfeilschifter@em.uni-frankfurt.de
Huwiler
A
A
D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D002518:Ceramides; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha