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. 1996 Jul 9;93(14):6959–6963. doi: 10.1073/pnas.93.14.6959

Ceramide-binding and activation defines protein kinase c-Raf as a ceramide-activated protein kinase.

A Huwiler 1, J Brunner 1, R Hummel 1, M Vervoordeldonk 1, S Stabel 1, H van den Bosch 1, J Pfeilschifter 1
PMCID: PMC38916  PMID: 8692926

Abstract

Interleukin 1 is the prototype of an inflammatory cytokine, and evidence suggests that it uses the sphingomyelin pathway and ceramide production to trigger mitogen-activated protein kinase (MAPK) activation and subsequent gene expression required for acute inflammatory processes. To identify downstream signaling targets of ceramide, a radioiodinated photoaffinity labeling analog of ceramide ([125I] 3-trifluoromethyl-3-(m-iodophenyl)diazirine-ceramide) was employed. It is observed that ceramide specifically binds to and activates protein kinase c-Raf, leading to a subsequent activation of the MAPK cascade. Ceramide does not bind to any other member of the MAPK module nor does it bind to protein kinase C-zeta. These data identify protein kinase c-Raf as a specific molecular target for interleukin 1 beta-stimulated ceramide formation and demonstrate that ceramide is a lipid cofactor participating in regulation of c-Raf activity.

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Selected References

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