| First Author | Wiegmann K | Year | 1999 |
| Journal | J Biol Chem | Volume | 274 |
| Issue | 9 | Pages | 5267-70 |
| PubMed ID | 10026132 | Mgi Jnum | J:53251 |
| Mgi Id | MGI:1331568 | Doi | 10.1074/jbc.274.9.5267 |
| Citation | Wiegmann K, et al. (1999) Requirement of FADD for tumor necrosis factor-induced activation of acid sphingomyelinase. J Biol Chem 274(9):5267-70 |
| abstractText | The generation of mice strains deficient for select members of the signaling complex of the 55-kDa tumor necrosis factor receptor (TNF-R55) has allowed the assignment of specific cellular responses to distinct TNF-R55-associated proteins. In particular, the TNF-R55-associated protein FADD seems to be responsible for recruitment and subsequent activation of caspase 8. In this report we demonstrate the requirement of FADD for TNF-induced activation of endosomal acid sphingomyelinase (A-SMase). In primary embryonic fibroblasts from FADD-deficient mice the activation of A-SMase by TNF-R55 ligation was almost completely impaired. This effect is specific in that other TNF responses like activation of NF-kappaB or neutral (N-)SMase remained unaffected. In addition, interleukin-1-induced activation of A-SMase in FADD-deficient cells was unaltered. In FADD-/- embryonic fibroblasts reconstituted by transfection with a FADD cDNA expression construct, the TNF responsiveness of A-SMase was restored. The results of this study suggest that FADD, in addition to its role in triggering a proapoptotic caspase cascade, is required for TNF-induced activation of A-SMase. |
