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

• DOI: 10.1073/pnas.93.14.6959
• Publication Date: 2002-07-26T14:35:50Z
• Authors: A Huwiler; J Brunner; R Hummel; M Vervoordeldonk; S Stabel; H van den Bosch; J Pfeilschifter
• Keywords: c-Raf; MAP2K7; ASK1

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