| Stable expression of a dominant negative form of the FAN protein ( factor associated with neutral sphingomyelinase activation ) , which has been reported to mediate tumor necrosis factor induced activation of neutral sphingomyelinase , significantly inhibited CD 40 ligand induced sphingomyelinase stimulation and apoptosis of transformed human fibroblasts . ^^^ CD 40 signals apoptosis through FAN regulated activation of the sphingomyelin ceramide pathway . ^^^ Transformed fibroblasts from FAN knockout mice were also protected from CD 40 mediated cell death . ^^^ Finally , anti CD 40 antibodies were able to co immunoprecipitate FAN in control fibroblasts but not in cells expressing the dominant negative form of FAN , indicating interaction between CD 40 and FAN . ^^^ Altogether , these results strongly suggest that CD 40 ligation can activate via FAN a neutral sphingomyelinase mediated ceramide pathway that is involved in the cell growth inhibitory effects of CD40 . . ^^^ |